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PubMed1999

High prevalence of manifestations of gastric autoimmunity in parietal cell antibody-positive type 1 (insulin-dependent) diabetic patients. The Belgian Diabetes Registry.

Previous studies have shown a high prevalence of gastric parietal cell antibodies (PCA) in type 1 diabetes, which can be accompanied by (sub)clinical autoimmune gastric disease. This study aimed to determine the grade of associated autoimmunity and to assess the pattern of prevalence of PCA by gender, age, duration of disease, age at onset of diabetes, and human leukocyte antigen (HLA) type in an adult type 1 diabetic population. Furthermore, to examine the clinical significance of being PCA positive, manifestations of gastric autoimmune disease were studied in PCA-positive and PCA-negative patients. The population studied consisted of 497 type 1 diabetics (men/women, 252/245; mean age, 40.8 +/- 12.1 yr; mean duration of disease, 16.4 +/- 10.4 yr; mean age at onset, 26.9 +/- 13.5 yr; mean hemoglobin A1c, 8.1 +/- 1.6%). Associated autoantibodies were present in 39% and PCA were present in 20.9% of the subjects, particularly in older patients. Gender, duration, and age at onset of diabetes did not influence the appearance of PCA. Antithyroid peroxidase antibodies (aTPO) were more frequent in PCA-positive patients than in those without PCA (33.6% vs. 22.4%; P = 0.025), suggesting an association between gastric and thyroid autoimmunity. We could demonstrate an association between PCA and the HLA DR5 haplotype (P = 0.001) as well, but not with HLA DR3 and/or DR4. In the PCA-positive group, iron deficiency anemia was detected in 15.4%, and pernicious anemia was found in 10.5% of subjects. These autoimmune gastric manifestations were significantly more prevalent in PCA-positive diabetics than in PCA-negative subjects, in whom the percentages were 6.9% and 0.5%, respectively (P = 0.01 and P < 0.0001). PCA were prevalent in 84.6% of patients with pernicious anemia. A gastroscopic and anatomopathological examination performed in a subgroup of 30 patients with gastric symptoms revealed atrophic gastritis in 13 of 14 PCA-positive patients and in 9 of 16 PCA-negative subjects (P = 0.04). PCA were present in 59.1% of patients with atrophic gastritis. In conclusion, a high prevalence of parietal cell antibodies and associated autoimmune gastric disease is present in PCA-positive type 1 diabetics, recommending its screening. Early detection of PCA and iron deficiency anemia, pernicious anemia, and atrophic gastritis and the subsequent care could reduce the morbidity of type 1 diabetes.

Adult↗

PubMed2001

Long-term outcome of interferon-alpha-induced thyroid autoimmunity and prognostic influence of thyroid autoantibody pattern at the end of treatment.

Thyroid autoimmunity and dysfunction have been widely reported as side effects of interferon-alpha (IFN-alpha) treatment, but the literature lacks data regarding the long-term course of these complications, clinical observation being limited to 6-12 months off therapy. Our study is the first that has aimed to evaluate the natural history of IFN-related thyroid autoimmunity during a 6.2-yr follow-up after the IFN-alpha withdrawal as well as to investigate the potential role of the autoantibody pattern at the end of treatment to predict the long-term outcome. Our study group included 114 patients (79 males, 35 females), mean age 48 yr (range 23-67 yr) with no preexisting thyroid disease, undergoing a 12-month treatment with recombinant IFN-alpha for C virus-related chronic active hepatitis. Thyroid autoimmunity (serum TgAb and TPOAb) and function (serum FT(4), FT(3), TSH) were retrospectively evaluated at the end of IFN therapy, 6 months after IFN withdrawal and after a median period of 6.2 yr (range 5.5-8.4 yr). At the end of treatment, 78 patients were negative for thyroid autoantibodies (Abs-) and all but one of them remained so for the following evaluations. The remaining 36 patients had thyroid autoantibodies (Abs+) at the end of treatment, and they subsequently showed a heterogeneous behavior: 16 patients remained Abs+ for the whole length of the study (persistent thyroiditis); 10 patients became Abs- 6 months off therapy but were again Abs+ 6.2 yr later (remitting/relapsing thyroiditis); 10 patients reverted to autoantibody negativity at different observation times (transient thyroiditis). The absence of thyroid autoantibodies at the end of treatment was a protective factor for the successive development of thyroiditis (odds ratio: 0.02, confidence interval (CI) 95%: 0-0.1). On the contrary, the positivity for TgAb and/or TPOAb at high titers at the end of IFN treatment was significantly related to the highest risk of having chronic thyroiditis (odds ratio: 17.3, CI 95%: 3.2-91.7 for TgAb levels > 50 degree percentile; odds ratio: 7.3, CI 95%: 1.5-35.2 for TPOAb levels > 50 degree percentile). None of the patients showed overt thyroid dysfunction throughout the study, whereas a subclinical hypothyroidism was found in 12 patients. In all 12 cases, the functional abnormality was accompanied by the presence of thyroid autoantibodies. Eight of these 12 patients belonged to the group with persistent thyroiditis (P < 0.05). The absence of thyroid autoantibodies at the end of treatment was a protective factor for the successive development of thyroid dysfunction (odds ratio: 0.06, CI 95%: 0.01-0.56). On the contrary, the positivity for both TgAb and TPOAb at the end of IFN therapy was significantly correlated with the highest risk of having subclinical hypothyroidism 6.2 yr. later (odds ratio: 38.7; CI 95%: 6.2-242). Our study demonstrates that in patients undergoing an IFN-alpha therapy for chronic hepatitis C and with no evidence of preexisting thyroid disease: 1) the negativity for thyroid autoantibodies after IFN treatment is a protective factor for the developing thyroid autoimmunity and/or dysfunction in following years; 2) the IFN-alpha-related thyroid autoimmunity is not a complete reversible phenomenon because some patients can develop chronic thyroiditis; 3) high autoantibody levels at the end of IFN therapy are related to the risk of having chronic thyroid autoimmunity; and 4) the coexistence of TgAb and TPOAb at the end of treatment is a predictive factor for the presence of thyroid dysfunction, even if subclinical, many years after IFN withdrawal.

Adult↗

PubMed1997

Autoantibodies to glutamic acid decarboxylase in three patients with cerebellar ataxia, late-onset insulin-dependent diabetes mellitus, and polyendocrine autoimmunity.

BACKGROUND: Glutamic acid decarboxylase (GAD) is the main target of humoral autoimmunity in stiff-man syndrome (SMS) and insulin-dependent diabetes mellitus (IDDM). GAD autoantibodies (GAD-Abs) are reported in a few patients with cerebellar ataxia, but their relevance is unclear. We describe three patients with cerebellar ataxia and GAD-Abs. METHODS: GAD-Abs were assayed by radioimmunoassay (RIA) and immunohistochemistry and confirmed by immunoblot of recombinant human GAD65. The GAD-Ab levels of the three patients with cerebellar ataxia were compared with those of five with SMS, 49 with IDDM, 64 with cerebellar ataxia of probable degenerative origin without associated autoimmune features, 14 non-IDDM islet cell antibody-positive first-degree relatives of IDDM patients, and 91 normal subjects. RESULTS: The three patients with ataxia and GAD-Abs were women (mean age, 63 years) with an isolated progressive cerebellar disorder, family history of IDDM, late-onset IDDM, and several positive serum organ-specific autoantibodies. Two patients had autoimmune thyroiditis, and one had pernicious anemia. CSF analysis demonstrated oligoclonal IgG bands and intrathecal synthesis of GAD-Abs. By RIA, GAD-Ab titers from the three patients were similar to those of SMS and significantly higher, without overlap, than the titers of IDDM patients. GAD-Abs were absent in the 64 patients with cerebellar ataxia and no evidence of autoimmune disorders. CONCLUSIONS: These findings suggest a link of GAD autoimmunity not only with SMS but also with cerebellar dysfunction. GAD-Abs should be sought in patients with cerebellar ataxia who have late-onset IDDM and other organ-specific autoimmune manifestations.

Adolescent↗

PubMed1984

Practical versus theoretical management of autoimmune inner ear disease.

Autoimmune inner ear disease is an uncommon but distinct clinical entity. Our ignorance of the immune mediating pathways, need of further animal model experimentation, variability of laboratory test results and of patient treatment responses illustrate how poorly we understand this disorder. The purpose of this review is to compare practical vs theoretical management of autoimmune inner ear disease, based upon our current knowledge of the disease process and upon a review of clinical experience at the Cleveland Clinic Foundation. Representative case histories are presented. The following preliminary conclusions are discussed: Autoimmune inner ear disease can present as a systemic or localized otologic immune disorder. Hearing loss can begin at any age, with unilateral or bilateral sudden onset, fluctuating or progressive symptoms, with or without associated dizziness. The pathogenesis of autoimmune inner ear disease is probably multifactorial (cellular and humoral). The sensitivity and specificity of different laboratory tests vary greatly, but even the most sensitive tests may be falsely normal when symptoms are not acute or when the patient is taking immunosuppressant medication. The mainstay of autoimmune inner ear treatment is steroids: however, cytotoxic drugs are recommended when there is no response to steroid treatment. Apheresis is reserved for selected cases. Hearing improvement can be dramatic even after 2 months of profound deafness. Flare-ups of autoimmune ear disease are best managed by increasing steroid dosage or adding cytotoxic medications. Unfortunately, some patients will develop progressive hearing loss despite vigorous treatment.

Adolescent↗

PubMed1993

Mercury-induced renal autoimmunity: changes in RT6+ T-lymphocytes of susceptible and resistant rats.

The repeated administration of mercury to rats of the Brown Norway (BN) inbred strain results in a self-limiting production of autoantibodies to renal antigens (e.g., laminin) and autoimmune glomerulonephritis. In contrast, rats of the Lewis (LEW) strain do not develop renal autoimmunity after mercury treatment. Suppressor T-cells and/or the idiotype-anti-idiotype network have been implicated in the control of autoimmunity in susceptible (BN) rats as well as the "resistant" state of nonsusceptible (LEW) animals. In our investigations of the immune regulation of mercury-induced autoimmune glomerulonephritis, we have performed a phenotypic analysis of lymphocyte subpopulation in the spleens and lymph nodes of mercury-treated and control LEW, BN, and (BN x LEW) F1 hybrid rats. Of particular interest were RT6+ T-cells, a subpopulation of lymphocytes that may have immunoregulatory properties and show a relative decrease in mercury-treated BN rats concomitantly with the development of autoimmune responses to renal autoantigens. LEW rats did not develop renal autoimmunity after mercury treatment and had no significant change in the ratio of RT6+ to RT6- T-lymphocytes. Interestingly, the administration of mercury to (BN x LEW) F1 hybrid rats caused effects similar to those observed in the BN strain. Auto-immune responses to antigens of the kidney coincided with a change in the balance within the RT6 cell population, which was altered in favor of T-lymphocytes that do not express the RT6 phenotype.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1999

Evidence for the role of environmental agents in the initiation or progression of autoimmune conditions.

The concordance of autoimmune disease among identical twins is virtually always less than 50% and often in the 25-40% range. This observation, as well as epidemic clustering of some autoimmune diseases following xenobiotic exposure, reinforces the thesis that autoimmune disease is secondary to both genetic and environmental factors. Because nonliving agents do not have genomes, disease characteristics involving nonliving xenobiotics are primarily secondary to host phenotype and function. In addition, because of individual genetic susceptibilities based not only on major histocompatibility complex differences but also on differences in toxin metabolism, lifestyles, and exposure rates, individuals will react differently to the same chemicals. With these comments in mind it is important to note that there have been associations of a number of xenobiotics with human autoimmune disease, including mercury, iodine, vinyl chloride, canavanine, organic solvents, silica, l-tryptophan, particulates, ultraviolet radiation, and ozone. In addition, there is discussion in the literature that raises the possibility that xenobiotics may also exacerbate an existing autoimmune disease. In this article we discuss these issues and, in particular, the evidence for the role of environmental agents in the initiation or progression of autoimmune conditions. With the worldwide deterioration of the environment, this is a particularly important subject for human health.

Anilides↗

PubMed1999

The role of genetic factors in autoimmune disease: implications for environmental research.

Studies in both humans and in animal models of specific disorders suggest that polymorphisms of multiple genes are involved in conferring either a predisposition to or protection from autoimmune diseases. Genes encoding polymorphic proteins that regulate immune responses or the rates and extent of metabolism of certain chemical structures have been the focus of much of the research regarding genetic susceptibility. We examine the type and strength of evidence concerning genetic factors and disease etiology, drawing examples from a number of autoimmune diseases. Twin studies of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), type I diabetes, and multiple sclerosis (MS) indicate that disease concordance in monozygotic twins is 4 or more times higher than in dizygotic twins. Strong familial associations (odds ratio ranging from 5-10) are seen in studies of MS, type I diabetes, Graves disease, discoid lupus, and SLE. Familial association studies have also reported an increased risk of several systemic autoimmune diseases among relatives of patients with a systemic autoimmune disease. This association may reflect a common etiologic pathway with shared genetic or environmental influences among these diseases. Recent genomewide searches in RA, SLE, and MS provide evidence for multiple susceptibility genes involving major histocompatibility complex (MHC) and non-MHC loci; there is also evidence that many autoimmune diseases share a common set of susceptibility genes. The multifactorial nature of the genetic risk factors and the low penetrance of disease underscore the potential influence of environmental factors and gene-environment interactions on the etiology of autoimmune diseases.

Animals↗

PubMed1999

Occupational exposure to crystalline silica and autoimmune disease.

Occupational exposure to silica dust has been examined as a possible risk factor with respect to several systemic autoimmune diseases, including scleroderma, rheumatoid arthritis, systemic lupus erythematosus, and some of the small vessel vasculitidies with renal involvement (e.g., Wegener granulomatosis). Crystalline silica, or quartz, is an abundant mineral found in sand, rock, and soil. High-level exposure to respirable silica dust can cause chronic inflammation and fibrosis in the lung and other organs. Studies of specific occupational groups with high-level silica exposure (e.g., miners) have shown increased rates of autoimmune diseases compared to the expected rates in the general population. However, some clinic- and population-based studies have not demonstrated an association between silica exposure and risk of autoimmune diseases. This lack of effect may be due to the limited statistical power of these studies to examine this association or because the lower- or moderate-level exposures that may be more common in the general population were not considered. Experimental studies demonstrate that silica can act as an adjuvant to nonspecifically enhance the immune response. This is one mechanism by which silica might be involved in the development of autoimmune diseases. Given that several different autoimmune diseases may be associated with silica dust exposure, silica dust may act to promote or accelerate disease development, requiring some other factor to break immune tolerance or initiate autoimmunity. The specific manifestation of this effect may depend on underlying differences in genetic susceptibility or other environmental exposures.

Arthritis, Rheumatoid↗

PubMed2006

State of the art. Four easy pieces: interconnections between tissue injury, intermediary metabolism, autoimmunity, and chronic degeneration.

Four questions are posed: (1) Can tissue damage itself provoke autoimmunity? (2) Can genetic mutations of key structures produce tissue pathology and thus provoke autoimmunity? (3) Can acute immune damage produce tissue degeneration without further hallmarks of an immune response? (4) Can intermediary metabolism modulate immune damage to tissues? Four answers are given: (1) Tissue injury itself may lead to autoimmunity. Both innate and adaptive immunity may arise as a response to tissue injury, and the immune attack can further damage tissue. (2) Genetic mutations can lead to an immune response indistinguishable from autoimmunity, exemplified from Duchenne's Muscular Dystrophy and X-linked adrenoleukodystrophy. (3) Chronic immune damage may lead to tissue degeneration, with or without further hallmarks of an immune response. Variations on this theme, including inverse scenarios, are also possible: Inborn errors of metabolism may lead to tissue damage that may provoke an adaptive and or innate immune response. The immune response might further damage tissue. (4) Finally, perturbations of intermediary metabolism may modulate the immune response, controlling the extent of immune-mediated damage. Examples are taken from perturbations in the cholesterol pathway that influence the characteristics of the immune response, and with tryptophan metabolites that modulate autoimmunity and graft rejection. Inflammatory, degenerative, and autoimmune neurological disease will be discussed in terms of their implications for pathogenic mechanisms underlying chronic obstructive pulmonary disease.

Adrenoleukodystrophy↗

PubMed1996

IDDM and autoimmune thyroid disease in the pediatric age group.

Diabetic patients have increased chances of developing autoimmune thyroid disease. Thyroid autoantibodies (Th-AAb) are more frequent in IDDM children than in the general population, ranging between 7 and 40%. As markers of thyroid autoimmunity, we assessed Th-AAb (MsA and TgA) cross-sectionally in 212 children and adolescents (93 girls and 119 boys) aged 1.2-21 years with IDDM from 0-18 years, and longitudinally in 90/212 (43 girls and 47 boys) at diagnosis and during a 3-10 year follow-up. In the cross-sectional study Th-AAb were found in 22/93 girls (23.7%) and 13/119 boys (10.9%). In the longitudinal study Th-AAb were observed at diagnosis in 6 patients, and during the follow-up in 9 girls. In 11/15 Th-AAb positive patients anti-nuclear antibodies were also present. Hormonal assessment revealed hypothyroidism in 3 girls (afterwards on replacement therapy), thyroid ultrasonography showed abnormal patterns in 5 girls, fine needle aspiration biopsy confirmed Hashimoto's thyroiditis in 9 (8 girls and 1 boy), with a higher frequency than that reported among healthy subjects (1-2%). Thyrotoxicosis also occurs with increased frequency in diabetic children than in the general population. We observed Graves' disease in only 1/212 IDDM patients, a 13 year-old boy in whom thyrotoxicosis developed 4 years after diabetes was diagnosed. The high prevalence of thyroid autoimmunity in our patients, particularly in females, suggests that diabetic children and adolescents should be screened for thyroid autoimmunity even if asymptomatic for hypo- or hyperthyroidism. Patients with IDDM and autoimmune thyroid disease should be evaluated for autoantibodies against other organs, such as adrenal glands and gastric mucosa. It is known that patients affected by type 1 (insulin-dependent) diabetes mellitus (IDDM) may have autoantibodies against different organs, such as thyroid, adrenal glands, gastric mucosa, parathyroid, with or without evident dysfunction of the target organ /1-8/. Among organ-specific disorders, autoimmune thyroid disease (ATD) is frequently associated with IDDM and the presence of thyroid autoantibodies (Th-AAb) has been considered a risk factor for the development of hypo- or hyperthyroidism /9/.

Adolescent↗

PubMed2004

Prevalence of 20S proteasome, anti-nuclear and thyroid antibodies in young patients at onset of type 1 diabetes mellitus and the risk of autoimmune thyroiditis.

Patients with type 1 diabetes mellitus (DM1) are at high risk to develop further autoimmune disorders, which are mostly characterized by the presence of organ-specific antibodies in serum and a subclinical disease course. Diabetes-related (glutamic acid decarboxylase, tyrosine phosphatase, IA-2) and thyroid-specific (thyroperoxidase, thyroglobulin) as well as antibodies to 20S proteasome, and anti-nuclear antibodies, were measured at DM1 onset in 147 children and adolescents. Patients were followed prospectively for the development of autoimmune thyroiditis (TSH elevation and/or sonographic thyroid gland enlargement in the presence of thyroid antibodies) up to 12 years, median observation time 4.4 years. Eight of 147 (5.4%) patients developed autoimmune thyroiditis. The cumulative incidence (+/-SE) at 5 years was 0.08+/-0.03. The prevalence of thyroid antibodies was 16.7%, of DM-related 88.4%, 20S proteasome 21.9%, and anti-nuclear antibodies 20.0%. There was a positive correlation between thyroid and anti-nuclear antibodies (p <0.001). Clinical course of DM1 and remission duration were not influenced by the presence of autoantibodies. However, in contrast to patients without antibodies, those with positive antibodies had significantly (p <0.001) elevated cumulative incidence of autoimmune thyroiditis at 5 years: thyroperoxidase 0.40+/-0.13, thyroglobulin 0.38+/-0.15, and anti-nuclear antibodies 0.29+/-0.12, respectively. These data underline that autoimmunity in patients with DM1 is not only restricted to beta-cell antigens at the onset of disease. In particular, patients with positive thyroid and anti-nuclear antibodies are at high risk to develop autoimmune thyroiditis during the first 5 years of DM1.

Adolescent↗

PubMed2005

B cells and autoimmunity 2004: new concepts and therapeutic perspectives.

Recently, studies of B-cell physiology have continued to provide new and surprising insights into the nature of autoimmunity, highlighting novel potential immunointervention strategies. The meeting on 'B cells and autoimmunity: new concepts and therapeutic perspectives' brought together basic scientists and clinicians with research interests in a range of autoimmune diseases. Recent advances in different facets of B-cell biology were discussed in the prospect of understanding autoimmunity, and significant advances in our understanding of the mechanisms that regulate the autoimmune response at the B cell-level were described. Even though no single message emerged, it is clear that the B lymphocyte is truly destined to become a therapeutic target for the treatment of autoimmune disease.

Animals↗

PubMed1987

Concept of a multigenic basis for the pathogenesis of spontaneous autoimmune thyroiditis.

The review presents a concept for the pathogenesis of spontaneous, organ-specific autoimmune diseases that take into account an altered immune regulation, modulating hormonal influences and a genetically determined primary susceptibility of the target organ for the autoimmune attack. The concept is exemplified by means of the Obese strain (OS) chicken model which develops a spontaneous hereditary autoimmune thyroiditis. In respect to the the altered function of the immune system both, MHC associated (Ir) and non-MHC associated genes are involved. The MHC, i.e. a certain haplotype, only plays a modulatory role in determining the frequency and severity of spontaneous autoimmune thyroiditis, while the presence of certain non-MHC associated genes is a absolute prerequisite for the emergence of the disease. The latter is also true for the genetically determined target organ susceptibility, while hormonal factors, notably sex-steroids and glucocorticoids, again only have a facultative, modulatory effect. Only if an appropriate genetic constellation concerning the non-MHC encoded aberrant immunological function and genes coding for the susceptibility of the thyroid gland for the autoimmune process is present, severe autoimmune thyroids develops.

Animals↗

PubMed1999

Lipoprotein (a) levels, apolipoprotein (a) phenotypes and thyroid autoimmunity.

It has been reported that euthyroid normolipidemic males and postmenopausal females exhibit significantly higher serum lipoprotein (a) (Lp(a)) levels compared with age- and sex-matched normolipidemic controls. However, it is well known that there is an inverse correlation between Lp(a) concentration and apolipoprotein (a) (apo(a)) isoform size. Thus, it is imperative to exclude differences in apo(a) isoform frequencies between subjects with or without thyroid autoimmunity in order to verify if there is an association between thyroid autoimmunity and increased Lp(a) concentration. To exclude such an effect of different apo(a) isoform frequencies, we determined apo(a) phenotypes in 22 patients (9 males and 13 postmenopausal females) with thyroid autoimmunity and in 64 (29 males and 35 females) age- and sex-matched individuals without thyroid autoimmunity (control group). There were no significant differences in the values of lipid parameters between the two groups, including Lp(a). We did not detect any significant differences in the apo(a) phenotype frequencies between the two groups. Additionally, in neither of the subgroups formed according to the presence of low molecular vs high molecular weight apo(a) isoforms were there any significant differences in median serum Lp(a) levels between patients with and without thyroid autoimmunity. Thus, our results contradict the previously reported association between thyroid autoimmunity and Lp(a) concentrations.

Adult↗

PubMed2003

Autoimmune thyroid disease: propagation and progression.

Autoimmune thyroid disease is the archetype for organ-specific autoimmune disorders. Progress in treating these disorders lies in improvements of our understanding of the predisposing factors responsible, the mechanisms responsible for progression of disease, and the interaction between thyroid antigens and the immune system at the level of the T cell and antibody. In common with other autoimmune diseases, genetic, environmental and endogenous factors are required in an appropriate combination to initiate thyroid autoimmunity. At present the only genetic factors which have been confirmed lie in the HLA complex and CTLA-4 or a closely linked gene. Identifying other predisposing genes will require large-scale family studies, or further insights into likely candidate genes. A number of environmental factors are known to predispose to autoimmune thyroid disease, including smoking, stress and iodine intake, while immunomodulatory treatments are revealing new pathways for disease emergence. The thyroid cell itself appears to play a major role in disease progression, interacting with the immune system through expression of a number of immunologically active molecules including HLA class I and II, adhesion molecules, cytokines, CD40 and complement regulatory proteins. New techniques, in particular phage display libraries, are providing the methods with which to identify autoantibody diversity in autoimmune thyroid disease and to provide tools for mapping autoantigenic epitopes. Application of these techniques is likely to lead to an understanding of how TSH receptor antibodies interact with the receptor to cause Graves' disease and also to the identification of novel orbital autoantigens in thyroid-associated ophthalmopathy.

Disease Progression↗

PubMed1992

[Relationship between autoimmune diseases and pneumoconiosis].

In recent years, with the aging of patients with pneumoconiosis, autoimmune diseases as a complication have been observed. One of the reasons for this may be that autoimmune diseases are prone to develop among the elderly. On the other hand, it has been reported that dust itself, such as silica for example, has adjuvant effect. A review of the recent literature published in Japan and abroad was made to clarify the relationship between pneumoconiosis and autoimmune diseases and the following results were obtained. 1) Disorders which accompany pneumoconiosis: Scleroderma, rheumatoid arthritis, systemic lupus erythematosus (SLE), and disorders of the kidney and liver have been reported. In Japan, about 30 cases of pneumoconiosis accompanied with autoimmune diseases have been reported. In many of the reports, patients with pneumoconiosis and scleroderma have a past history of exposure to silica. In both case studies and case control studies, patients with rheumatoid arthritis and history of silica exposure are prone to develop pneumoconiosis. 2) Immunological studies of patients with pneumoconiosis: As for humoral immunity, elevation of polyclonal gamma-globulin, especially IgG, has been often reported together with high positive rate of autoantibodies such as antinuclear antibodies. In cellular immunity, decreased delayed type skin reaction and decreased CD4/8 ratio have been reported. In human leukocyte antigen (HLA) typing the elevated frequency of DR4 has been reported. In the study of BAL increased production of superoxide anion O2- by alveolar macrophages has been observed. 3) EXPERIMENTAL STUDIES: Silica is well known for its toxicity to cells and also for its adjuvant effect. In the German Democratic Republic, patients with scleroderma and history of long term silica exposure are recognized as patients with occupational disease even though pneumoconiosis is not clearly demonstrated on X-ray film. It is difficult from this review to nrake a definite conclusion regarding the relation between silicosis and autoimmune diseases. There is a need to repeat this review of the literature on autoimmune diseases and pneumoconiosis in the near future.

Aging↗

PubMed1994

Immunoglobulin variable-region structures in immunity and autoimmunity to DNA.

Important to the immunopathology associated with the autoimmune disease systemic lupus erythematosus, is the production of autoantibody to DNA. Crucial to understanding the immunological basis for autoimmunity to DNA is knowing whether the anti-DNA autoantibody is the product of clonally-selective, antigen-specific B cell stimulation or non-selective, polyclonal B cell activation. Structural analyses of the immunoglobulin variable-regions of both early, IgM and late, IgG anti-DNA antibodies from lupus-prone (NZB x NZW) F1 mice have indicated that both IgM and IgG anti-DNA autoantibodies are generated by clonally-selective B cell stimulation. Within individual autoimmune mice the later appearing, IgG anti-DNA autoantibodies are structurally similar to the earlier appearing, IgM antibodies, and in some cases both IgM and IgG may be produced by the same B cell clones. The variable-region structural data also suggest that DNA or complexes containing DNA may be the immunogenic stimuli for autoantibody to DNA. In support of this conclusion, normal mice immunized with immunogenic peptide-DNA complexes produce anti-DNA antibodies with structural and serological characteristics similar if not identical to those of autoimmune anti-DNA antibodies. Normal mice immunized with peptide-DNA complexes eventually develop immunopathology that resembles lupus nephritis. These results suggest that autoimmunity to DNA and subsequent autoimmune disease in SLE may result from a specific immune response to DNA containing antigens.

Animals↗

PubMed2004

Intravenous immunoglobulin plus interferon-alpha in autoimmune hepatitis C.

BACKGROUND: Hepatitis C virus (HCV) may be associated with a variety of autoimmune phenomena causing a therapeutic dilemma for treatment with interferon-alpha (IFNalpha), which stimulates autoimmune symptoms, or with corticosteroids, which may lead to an increasing of viral load. To evaluate the possible role of intravenous immunoglobulins (IVIg) in the response of patients treated with IFNalpha, we administered IVIg plus IFNalpha and compared the results with a group of patients treated with IFNalpha alone. METHODS: Forty-two patients affected by chronic hepatitis C with probable autoimmune disease were eligible for this open-label, randomised study. All patients tested positively for anti-nuclear antibodies, anti-smooth muscle antibodies, anti-liver/kidney microsomal antibodies and anti-mitochondrial antibodies. Patients were randomly assigned to one of two groups: group A received IVIg at a dosage of 400 mg/kg each day for 5 days, and then 3 MUI of leucocyte IFNalpha three times a week, while group B received physiological solution followed by the administration of leucocyte IFNalpha three times a week at the same dosage for 6 months. Complete biochemical response was defined as a sustained normalisation of alanine aminotransferase levels, and complete virological response was defined as complete clearance of virus throughout the entire 6-month follow-up period. Immunological response was measured in terms of Autoimmune Hepatitis (AIH) score, while histological response was based on a reduction in histological activity index (HAI) score. RESULTS: Compared with patients receiving IFNalpha alone, a higher percentage of patients who received IFNalpha plus IVIg showed complete virological and histological responses (p = 0.04). More patients in the combination therapy group achieved biochemical and immunological responses, although the differences between the groups were not statistically significant at all time points. CONCLUSIONS: Exogenously added Ig might modulate the immune network at various points. We propose that the immunomodulating action of IVIg acts synergistically with IFNalpha, achieving a better response to IFN treatment in patients with chronic HCV associated with autoimmunity. Data obtained from this preliminary study indicate a positive prospective for the clinical use of gamma globulins in patients with a high probability of autoimmune disorders associated with HCV infection.

Alanine Transaminase↗