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PubMed2001

[Autoimmune thyroiditis].

The continuum of clinical phenotype between different autoimmune thyroid diseases and mainly the common pathophysiological mechanisms have lead to a novel classification of these disorders into three types: (1) Type 1 autoimmune thyroiditis (euthyroidism associated with the presence of anti-thyroglobulin and anti-thyroperoxydase autoantibodies); (2) Type 2 autoimmune thyroiditis or Hashimoto's disease (hypothyroidism with anti-thyroglobulin and anti-thyroperoxydase autoantibodies). Postpartum thyroiditis falls into this category and is characterized by transient hyperthyroidism followed by hypothyroidism; and (3) Type 3 autoimmune thyroiditis or Graves-Basedow's disease (hyperthyroidism with anti-TSH receptor "stimulating" auto-antibodies, often associated with anti-thyroglobulin and anti-thyroperoxydase autoantibodies). Thyroid orbitopathy often complicates Type 3 autoimmune thyroiditis and is thought to result from an autoimmune response against an autoantigen common to thyroid and orbital fibroblasts/adipose cells. We present the actualized knowledge about the immunological parameters that can be detected and quantified in autoimmune thyroid diseases, about the pathophysiological mechanisms involved in these disorders, and about the options of their treatment that are currently offered to the medical community.

Biomarkers↗

PubMed2001

Excess autoimmune disease mortality among school teachers.

OBJECTIVE: To investigate evidence of an association between school teaching and mortality from autoimmune diseases. METHODS: A proportional mortality study using US death certificates from the 1985-95 period was conducted. Death certificates that listed elementary or secondary school teaching as the usual occupation were identified, as were those that cited any of 13 autoimmune diseases as a cause of death. Proportional mortality ratios (PMR) were calculated to compare autoimmune disease mortality among teachers to that among persons in other professional occupations. RESULTS: The PMR for total autoimmune disease mortality among teachers was 113 (p < 0.0001). Rheumatic diseases accounted for 53.1% of the total excess in mortality and multiple sclerosis accounted for 39.9%. Significantly elevated autoimmune disease mortality occurred for female teachers (PMR = 111, p < 0.0001), male teachers (PMR = 124, p < 0.0001), white teachers (PMR = 112, p < 0.0001), non-white teachers (PMR = 118, p = 0.005), elementary teachers (PMR = 111, p < 0.0001), and secondary teachers (PMR = 130, p < 0.0001). There was an inverse trend (p < 0.0001) in the level of excess mortality relative to age. PMR were 149, 144, 127, 118, 108, and 102 for teachers in the 35-44, 45-54, 55-64, 65-74, 75-84, and > or = 85 year age groups, respectively. Excess mortality was significantly greater in secondary teachers than elementary teachers both in total (PMR = 112, p = 0.04) and in the 35-44 age group (PMR = 155, p = 0.03). CONCLUSION: Our results substantiate excess mortality from autoimmune diseases among teachers and suggest that, relatively early in their careers, teachers experience an occupational exposure that increases risk of autoimmune diseases.

Adult↗

PubMed2003

Autoimmune liver disease in children.

Autoimmune liver disorders are characterised by an inflammatory liver histology, circulating non-organ specific autoantibodies and increased levels of immunoglobulin G (IgG) in the absence of a known aetiology. They respond to immunosuppressive treatment, which should be instituted as soon as diagnosis is made. Liver disorders with a likely autoimmune pathogenesis include autoimmune hepatitis (AIH) and autoimmune sclerosing cholangitis (ASC). Two types of AIH are recognised according to seropositivity for smooth muscle and/or antinuclear antibody (SMA/ANA, type 1) or liver kidney microsomal antibody (LKM1, type 2). There is a female predominance in both. LKM1-positive patients tend to present more acutely, at a younger age, and commonly have immunoglobulin A (IgA) deficiency, while duration of symptoms before diagnosis, clinical signs, family history of autoimmunity, presence of associated autoimmune disorders, response to treatment and long-term prognosis are similar in both groups. The most common type of paediatric sclerosing cholangitis is ASC. The clinical, biochemical, immunological and histological presentation of ASC is often indistinguishable from that of AIH. In both, there are high IgG, non-organ specific autoantibodies and interface hepatitis. Diagnosis is made by cholangiography. Children with ASC respond to immunosuppression satisfactorily and similarly to AIH in respect to remission and relapse rates, times to normalisation of biochemical parameters and decreased inflammatory activity on follow-up liver biopsies. However, the cholangiopathy can progress and there may be an evolution from AIH to ASC over the years, despite treatment. Whether the juvenile autoimmune form of sclerosing cholangitis and AIH are 2 distinct entities, or different aspects of the same condition, remains to be elucidated.

Child↗

PubMed1992

The relationship between autoimmune thyroid disease and iodine intake: a review.

There is evidence to suggest that elevated levels of iodide in the diet are associated with autoimmune thyroid disease (ATD) in susceptible individuals, and that autoimmune thyroiditis (Hashimoto's disease) is less common in susceptible individuals who live in regions with dietary iodine deficiency. There are epidemiologic studies in endemic goiter areas that report an increase in ATD, particularly thyroiditis, after the therapeutic administration of iodized salt, bread and oil. Lymphocytic infiltration of the thyroid is rarely found in patients from severe endemic goiter regions, yet there is a reversal of this observation after dietary iodine supplementation. Thyroid antibodies, both thyroglobulin (TgAb) and peroxidase (TpAb) or microsomal, were not detected in serum from patients with endemic goiter, but became positive in 43% of subjects three and six months after therapy with iodized oil, and there developed transient hyperthyroidism. Similarly, the addition of iodine to the diet or the administration of iodine-containing medications increases the frequency of ATD and the severity of existing autoimmune thyroiditis. Furthermore, autoimmune thyroiditis has been induced by the administration of excess iodide to strains of chickens and rats that are genetically predetermined to develop the disease. We are beginning to understand the pathogenesis of ATD. In hyperthyroidism the evidence clearly supports the hypothesis that TSH receptor antibodies (TRAb) stimulate the TSH receptor to induce excessive and sustained secretion of thyroid hormones. Cellmediated immune mechanisms, such as antibody dependent cellmediated cytotoxicity (ADCC), initiate the lymphocytic infiltration and thyrocytotoxicity in autoimmune thyroiditis. The mechanisms that initiate the development of the abnormal immune response and the relationship of ATD with excess iodide are poorly understood. There is evidence that an increase in the iodination of thyroglobulin (Tg) enhances its immunogenicity. The results of clinical and experimental studies support the requirement of a genetic predisposition to the development of ATD that may be precipitated by exposure to certain environmental factors. Another mechanism supported by experimental data is the direct toxic effect of excess iodide on iodide-deficient thyroid glands. High concentrations of iodide after oxidation to iodine causes epithelial necrosis and inflammation associated with lipofuscin accumulation suggestive of toxicity mediated by lipid peroxidation from excessive amounts of free radicals. The epithelial damage would initiate inflammatory and immune responses. Although these mechanisms would relate to the onset of autoimmune thyroiditis on exposure to excessive amounts of iodide, the relationship of iodide intake and autoimmune hyperthyroidism is less clear.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMedDate not supplied

Immunohistochemical detection of Fas and apoptosis in type-1 autoimmune hepatitis.

BACKGROUND/AIMS: Although Fas expression has been reported in liver with chronic viral hepatitis and primary biliary cirrhosis, little is known about Fas expression and apoptosis in type-1 autoimmune hepatitis. The aim of this study was to investigate whether the expression of Fas and apoptosis are found in liver with autoimmune hepatitis. The relationship between Fas expression and clinicopathological findings including the occurrence of apoptosis was also investigated. METHODOLOGY: Fas expression and apoptosis were immunohistochemically examined in liver tissues from 20 patients with autoimmune hepatitis and five control subjects using specific antibodies against Fas and single-stranded DNA. The grade of expression of Fas and apoptosis was evaluated and compared with histological findings and the results of liver function tests in each patient. RESULTS: Fas expression in hepatocytes was detected in all patients with autoimmune hepatitis, while Fas expression was not detected in control livers. The Fas-positive hepatocytes were particularly abundant in those areas facing piecemeal and confluent necrosis. In 30% of autoimmune hepatitis cases, bile-duct cells were faintly stained for Fas. A few hepatocytes positive for single-stranded DNA were found in the areas facing piecemeal necrosis and confluent necrosis. In 95% cases, many bile-duct cells were positive for single-stranded DNA. No relationship between the expression of Fas and single-stranded DNA was found in hepatocytes or bile-duct cells. However, the degree of Fas expression in hepatocytes significantly correlated with serum transaminase concentrations and was increased in parallel with the grade of activity but not with the stage of fibrosis. CONCLUSIONS: We have demonstrated that Fas expression is detected in hepatocytes of the liver with autoimmune hepatitis and that the level of Fas expression reflects the severity of inflammation in autoimmune hepatitis.

Adult↗

PubMed2004

[Iodine and thyroid autoimmunity].

The pathogenetic mechanisms leading to the development of autoimmune disease of the thyroid are based on several different factors. The resultant immune response is related to both the genetic predisposition and other influencing factors such as iodine intake, a very important modulator of thyroid autoimmunity. To a large extent, the details of the mechanisms that induce the immune response and lead to chronic autoimmune thyroid reactions are still poorly understood. In genetically predisposed individuals the iodine intake modulates autoimmune thyroid reactions. Especially with acute or chronic increase of iodine intake it leads to a significant increase in the incidence and intensity of autoimmune thyroid disease. There is a need to further investigate whether the results of experimental animal studies can be generalised to humans. Epidemiological data from countries with sufficient or high nutritional iodine intake clearly show that in comparison to countries with iodine deficiency there is an increase in the incidence of autoimmune thyroid disease and a change in the pattern of manifestation, e.g. in the proportion of autoimmune thyroiditis and hyperthyroidism due to Graves' disease. At the same time, thyroid diseases related to iodine deficiency significantly decrease, which is to be expected with a continuously higher iodine intake.

Animals↗

PubMed2006

Atopic dermatitis and systemic autoimmune diseases: a descriptive cross sectional study.

Atopic dermatitis (AD) has a Th2 (T-helper 2) immune-reactivity pattern. However, the majority of systemic autoimmune diseases, such as rheumatoid arthritis, multiple sclerosis, and insulin dependent diabetes mellitus show a Th1 (T-helper 1) reactivity pattern. From this, one may hypothesize that AD and the Th1 autoimmune diseases could be inversely associated and AD may be more common in the minority of autoimmune diseases with a Th2 overactivity pattern such as systemic lupus erythematosus. A cross sectional study was designed. Our patients were enrolled from a general university hospital (all systemic autoimmune patients in every medical ward based on definite diagnoses in their medical records). Information on atopic dermatitis was obtained by questionnaires and physical examination by a dermatologist. A total of 63 patients were studied; 17.5 percent of cases had atopic dermatitis in the past or present. There were 31 patients 49.2 %) who carried a diagnosis known to be associated with Th1 reaction, and 21 patients (33.3 %) who had a disease associated with Th2-type reactivity. In 11 patients (17.5 %) the T-cell reaction type was not definitively classified. The relative frequency of AD was 9.7 percent (3 of 31 cases) in Th1-related autoimmune diseases, 28.6 percent (6 of 21 cases) in Th2-related autoimmune diseases and 18.2 percent (2 of 11 cases) in the unclassified category, a difference not statistically significant. Although the power of this study is not high enough to show a statistical significance, AD seems to be uncommon in patients with autoimmune diseases associated with Th1 overactivity.

Adolescent↗

PubMed2006

Characterization and differentiation of autoimmune versus viral liver involvement in patients with Sjögren's syndrome.

OBJECTIVE: To analyze the prevalence and clinical significance of liver involvement in patients with Sjögren's syndrome (SS), focusing on the characterization and differentiation of autoimmune versus chronic viral liver disease. METHODS: We investigated liver involvement (clinical signs, analytical data, chronic viral infections, and autoantibodies) in 475 consecutive patients with SS. All patients fulfilled 4 or more of the 1993 European Community Study Group criteria for SS. RESULTS: Liver involvement was detected in 129 (27%) patients. After ruling out chronic illnesses or use of hepatotoxic drugs, the main etiologies were chronic viral liver disease in 64 (13%) cases [chronic hepatitis C virus (HCV) infection in 63 and HBV infection in one] and autoimmune liver diseases in 24 (5%; primary biliary cirrhosis in 16 patients and type-1 autoimmune hepatitis in 8). The analytical liver profile was not useful in differentiating between viral and autoimmune liver disease. In contrast, patients with SS and autoimmune liver disease presented higher mean values of erythrocyte sedimentation rate (p = 0.044), circulating gammaglobulins (p = 0.007), and a higher prevalence of antinuclear antibodies (p < 0.001), antimitochondrial antibodies (p < 0.001), anti-smooth muscle antibodies (p = 0.026), anti-Ro/SSA (p < 0.001), and anti-La/SSB (p = 0.01), while patients with chronic viral liver disease had a higher frequency of cryoglobulinemia (p < 0.001) and hypocomplementemia (p < 0.001). CONCLUSION: Chronic viral liver disease (associated overwhelmingly with HCV) was the main cause of liver involvement in our patients with SS, with a prevalence of 13%, nearly 3-fold greater than that observed for autoimmune liver involvement. The immunological pattern played a key role in the differentiation of viral (predominance of cryoglobulins and low complement levels) and autoimmune (higher frequency of autoantibodies) liver involvement.

Autoantibodies↗

PubMed1991

Vitiligo in autoimmune thyroid disease.

The authors studied the association between vitiligo and autoimmune thyroid disease. Vitiligo was found in 20 of 293 patients with autoimmune thyroid disease (6.83%), 2 out of 227 patients with nonautoimmune thyroid disease (0.88%), and 3 out of 386 control group (0.78%). These results showed that vitiligo is closely associated with autoimmune thyroid disease (chi 2 = 24.33, p < 0.0001), but not with nonautoimmune thyroid disease. Prevalence of vitiligo in nonautoimmune thyroid disease was not different from that in control. Vitiligo in autoimmune thyroid disease was most frequently found on dorsum hands and forearms, and usually preceded the onset of thyroid disease. Four out of twenty patients with vitiligo associated autoimmune thyroid disease had another presumed autoimmune disease, that is, alopecia areata, alopecia totalis, and rheumatoid arthritis. These findings suggested that autoimmunity plays an important role in the pathogenesis of vitiligo.

Adult↗

PubMed1990

Drugs in autoimmune diseases.

Autoimmune diseases arise when autoimmunity or the loss of self tolerance results in tissue damages. Many mechanisms have been proposed for the origin of autoimmunity, including immunologic, viral, hormonal and genetic factors. All known parts of the immunological network are involved in causing immunopathologic symptoms. Therefore, more or less specific immunosuppressants are widely used in the treatment of autoimmune disorders which range from organ-specific, i.e. Hashimoto's thyroiditis, to non-organ-specific or systemic diseases, i.e. systemic lupus erythematosus. Unspecifically acting cytostatics do not only suppress autoimmune reactions but also create severe side-effects due to the impairment of immune responses against foreign antigens, leading, for example, to an increased risk of infections. Moreover, the genotoxic activity of cytostatics might induce malignancies. Corticosteroids are clinically well known and very active agents for the management of acute symptoms but different side-effects limit their use in the treatment of chronic diseases. Cyclosporin A has been an important step forward to a more specific prevention of organ transplant rejections and to the therapy of some autoimmune disorders. Modern approaches to immunosuppression include monoclonal antibodies directed against a variety of different determinants on immunocompetent cells. Ciamexone and Leflunomide which are in early clinical and preclinical development, respectively, might be interesting new drugs. Future immunopharmacologic drug research and development should lead to more specific, low molecular weight, orally active and chemically defined immunosuppressive compounds with good tolerability under long-term treatment of autoimmune diseases.

Adrenal Cortex Hormones↗

PubMed1986

Polyglandular autoimmunity.

Although target tissues or glands differ, several common threads have begun to emerge that link the diseases of the autoimmune endocrine syndromes. In the polyglandular syndrome type II, a defect resides in one of the genes of the major histocompatibility locus which, in concert with other gene(s), results in susceptibility. Genetic susceptibility is necessary but not sufficient to produce the disorder. This is illustrated by the lack of 100% concordance of disease in identical twins. This lack of concordance has led to the search for environmental influences or "triggers" of the autoimmune process. These "triggers" have not been well defined, but may include amiodarone or other iodine-containing medications for thyroid autoimmunity and congenital rubella for some patients with diabetes and thyroiditis. The autoimmune destruction of most target glands appears to be a slow process with a long preclinical prodrome that may last for years. During this period, autoantibodies, lymphocyte abnormalities, and subclinical endocrine defects are usually present. As knowledge of target antigens has progressed, it appears that despite polyendocrine disease, within each gland specific antigens are the targets of the autoimmune process. When the genetic defect(s) and environmental influences of organ specific autoimmunity are better understood, it may be possible to devise specific "replacement" or corrective therapies. In the absence of this knowledge, therapies directed at partial immunosuppression are currently being studied in Type I diabetes and Graves' ophthalmopathy. Given the similar features of many of the organ-specific autoimmune disorders, it is likely that if immunotherapeutic modalities are successful in one disease, they may be of benefit in related disorders.

Animals↗

PubMed1985

Oncogene expression in autoimmune mice.

Systemic autoimmune disease states are known to be associated with abnormal cell growth or differentiation. In the murine models of systemic lupus erythematosus (SLE), specific genotypes result in dysregulated growth of certain lymphocyte subpopulations. Although genes underlying autoimmune syndromes have been characterized by mendelian genetics, it has not yet been possible to characterize them at the molecular level. Recently, it has become clear that cellular proto-oncogenes can regulate cell growth and differentiation. Therefore, we have studied the expression of five different proto-oncogenes; myc, myb, abl, bas, and raf, in organs and cells of various autoimmune strains. These genes were selected because each has previously been associated with abnormal hemopoietic cell growth, and because each has been at least partially characterized at the molecular and functional level. We have found selective abnormal proto-oncogene expression associated with the characteristic abnormal cell growth or differentiation of lymphocytes of autoimmune mice. The lymph nodes of MRL-lpr/lpr mice are packed with unusual T cells. These had a marked increase in myb expression. There was a 20-40-fold increase in myb RNA in lymph nodes of lpr/lpr mice on several different genetic backgrounds. The gld/gld mouse has a very similar unusual T cell in the lymph nodes: it also had a comparable increase in myb RNA in the nodes. In contrast, myb expression was not elevated in the other autoimmune mouse strains lacking these abnormal T cells. Whereas such lpr/lpr mice had increased myb expression in the lymph nodes and splenic T cells, they had markedly subnormal myb expression in the thymus, an organ with high myb in normal and in the other autoimmune strains. These results suggest that one phase of intrathymic differentiation in other mice occurs in the periphery of lpr/lpr mice. The spleens of NZB and male BXSB mice had increased myc expression which was found to be associated with B cells upon cell separation. Similarly, increased bas and abl expression was associated with autoimmune B cells. The xid gene, which retards or prevents the expression of murine lupus by retarding B cell maturation, was associated in BXSB.xid, NZB.xid, and MRL-lpr/lpr.xid congenic mice with marked reduction in expression of myc, bas, and abl in the spleens containing B cells, but not of myb in the lpr/lpr.xid nodes containing primarily the unusual T cells. Raf expression was found to be associated in lpr/lpr and gld/gld mice with both the unusual T cells and splenic B cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1985

Abnormal stem cells in autoimmune-prone mice are responsible for premature thymic involution.

Autoimmune-prone mice show premature thymic involution, including morphological and functional abnormalities. To determine why the thymic abnormalities develop in autoimmune-prone mice, transplantation of the thymus and/or bone marrow was performed. When thymuses of newborn MRL/1 (H-2k) mice were grafted into C3H/HeN nu/nu(H-2k) mice, the engrafted thymuses did not show the abnormalities which characterize the thymus in the autoimmune-prone MRL/1 mice. By contrast, when thymuses of newborn C3H/HeN or MRL/n mice were grafted into MRL/1 mice, the engrafted thymuses developed after an interval of 3 months the same morphological abnormalities as were seen in MRL/1 mice. Thus, we can conclude that premature involution of the thymus in autoimmune-prone mice may not be a genetically determined abnormality intrinsic to the thymus, but rather an abnormality secondary to other events occurring in these mice. When bone marrow of young C3H/HeN nu/nu mice was transplanted into irradiated (850 rad) MRL/1 mice, neither thymic abnormalities nor autoimmune diseases developed. Therefore, it seem likely that abnormal stem cells in autoimmune-prone mice induce thymic abnormalities, and these, in turn, are associated with the development of autoimmune diseases.

Animals↗

PubMed1982

Cell cycle analysis of lymphocyte activation in normal and autoimmune strains of mice.

The spontaneous spleen cell proliferation and the proliferation induced by in vivo or in vitro stimulation with such polyclonal B cell activators (PBA) as LPS, poly rI.rC, and anti-mu were studied in normal and autoimmune mice. The various murine models of autoimmunity differ in the level of naturally occurring splenic cellular hyperactivity as well as in the ability of their spleen cells to be further stimulated in vitro by polyclonal stimulators. Both the NZB strain and the MRL/Ipr strain had markedly increased numbers and percentages of spontaneously proliferating spleen cells, whereas the BXSB strain did not. Nonautoimmune strains were found to have very small numbers of activated cells in the spleen. However, such normal strains could be induced in vivo to mimic the natural splenic hyperactivity observed in older NZB and MRL/Ipr autoimmune strains by the injection of polyclonal B lymphocyte stimulators. In contrast, old hyperactive NZB mice were not further induced to undergo proliferation by in vivo administration of such stimulators. Density-separated, T depleted, spleen cells of normal and autoimmune mice were stimulated in vitro with PBA in 48-hr cultures. Cells from old MRL/Ipr and NZB mice were abnormal in both the anti-mu response and the LPS response; BXSB mice had normal anti-mu responses. These studies suggest that there is no prerequisite for spontaneous splenic hyperactivity in the development of autoimmunity. In addition, different PBA stimulate separate subsets of B cells that differ in their state of activation in the various autoimmune strains. Finally, different B cell subsets appear to be abnormal in different types of autoimmune mice.

Aging↗

PubMed1983

Abnormal binding of soluble IgG immune complexes to hepatic nonparenchymal cells of autoimmune mice.

Because the liver is the major organ responsible for removal of soluble immune complexes (IC), the surface binding characteristics of preformed model IC to unstimulated mouse liver nonparenchymal cells (NPC) in suspension were studied. NPC of non-autoimmune C3H/FeJ, C3H/HeJ, A/J, DBA/2 and the autoimmune NZB/W F1 and MRL/lpr female mice of various ages were isolated by perfusion of the portal vein with collagenase followed by separation of NPC from hepatocytes with a metrizamide gradient. Thirty-five percent of NPC of all mouse strains were nonspecific esterase-positive and phagocytosed latex beads. Radiolabeled mouse IgG anti-DNP covalently cross-linked stable IC were separated by gel filtration and bound to NPC under various conditions. Marked differences were noted in maximal number of IC bound per cell between the autoimmune and non-autoimmune mouse strains: 3.3 to 4.0 X 10(5) in the non-autoimmune strains vs 0.3 to 1.4 X 10(5) molecules of IC bound per cell in the autoimmune strains at 1 to 6 mo. Insignificant differences were noted in Ka by Scatchard plot analysis (3.5 to 5.0 X 10(8) M-1) and rate of reversibility of binding as determined by dissociation of surface-bound IC with an excess of heat-aggregated gamma-globulin (T 1/2:1.5 to 2 min). These data demonstrate a decreased number of available binding sites for IC in unstimulated NPC from NZB/W F1 and MRL/lpr female mice throughout their life spans. Although the findings are consistent with saturation of binding sites of the NPC with native IC, the abnormality found in the 1-mo-old autoimmune mice (who do not have detectable autoantibodies) suggests a primary defect in FC receptor expression or an altered state of activation of NPC that may contribute to the disease process.

Animals↗

PubMed1994

Autoimmune myelofibrosis. A steroid-responsive cause of bone marrow fibrosis associated with systemic lupus erythematosus.

Autoimmune myelofibrosis is an uncommon disorder in which patients present with anemia and thrombocytopenia in conjunction with limited clinical manifestations of autoimmune disease or an exacerbation of previously established SLE. The presence of leukoerythroblastosis in a patient with SLE may suggest the presence of myelofibrosis. Conversely, the absence of splenomegaly in a patient with presumed idiopathic myelofibrosis may suggest an autoimmune etiology. Patients with autoimmune myelofibrosis universally have a positive ANA test and frequently have either elevated anti-DNA titers or a positive LE cell preparation. Because physical manifestations of autoimmune disease may not be evident at presentation, all patients found to have myelofibrosis should have an ANA test. Peripheral blood cytopenias in autoimmune myelofibrosis frequently respond to glucocorticoids but regression of bone marrow fibrosis may be incomplete. Hematologic response to treatment parallels that of the associated autoimmune disease.

Adolescent↗

PubMed1993

Prevalence and characterization of neutrophil cytoplasmic antibodies in autoimmune liver diseases.

To evaluate the diagnostic significance of neutrophil cytoplasmic antibodies in chronic liver diseases, we assessed the prevalence of neutrophil cytoplasmic antibodies in autoimmune liver diseases, in particular in primary sclerosing cholangitis, autoimmune chronic active hepatitis and primary biliary cirrhosis, and we also determined the specificity of perinuclear-pattern neutrophil cytoplasmic antibodies for these autoimmune liver diseases by testing sera from patients with nonautoimmune chronic liver diseases. Neutrophil cytoplasmic antibodies were detected in 79% of sera from patients with primary sclerosing cholangitis (n = 24), in 88% of sera from patients with autoimmune chronic active hepatitis (n = 24) and in 28% of sera from patients with primary biliary cirrhosis (n = 25). The presence of neutrophil cytoplasmic antibodies in these diseases correlated significantly (p < 0.008) with the presence of cirrhosis. Neutrophil cytoplasmic antibodies were not detected in nonautoimmune liver diseases. All neutrophil cytoplasmic antibody-positive sera produced a perinuclear fluorescence pattern on ethanol-fixed granulocytes. On neutrophils fixed with paraformaldehyde, a granular cytoplasmic immunofluorescence pattern was observed, demonstrating the cytoplasmic nature of the antigen or antigens involved. Further characterization studies showed that neutrophil cytoplasmic antibodies in autoimmune liver diseases are not directed against myeloperoxidase, proteinase 3 or elastase, the neutrophil cytoplasmic antibody specificities associated with necrotizing vasculitis, glomerulonephritis or both. On Western blots neutrophil cytoplasmic antibodies in autoimmune liver diseases showed reactivity with either lactoferrin, a 67/66-kD protein combination or a 40-kD polypeptide. Reactivity with either of these proteins was observed in sera from patients with primary sclerosing cholangitis (38%), autoimmune chronic active hepatitis (17%) and primary biliary cirrhosis (20%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1997

Mapping of a gene for the increased susceptibility of B1 cells to Mott cell formation in murine autoimmune disease.

Mott cells, a pathologic state of plasma cells containing intracellular inclusions of Igs (Russell bodies), are frequent in lymphoid tissues of murine and human autoimmune diseases. However, neither the genesis nor the significance of Mott cells in autoimmune diseases is well understood. We found that B1, but not B2, cells were induced in vitro to form Mott cells in the presence of LPS or IL-5, but not other stimulants, in a much higher frequency in autoimmune New Zealand Black (NZB) and NZB x New Zealand White (NZB/W) F1 than in non-autoimmune disease-prone mice and notably athymic nude NZB/W F1 mice. Cell surface phenotypes of Mott cells were B220+ CD5+ CD43+ CD11b(dull), while those of peritoneal macrophages were B220- CD5- CD43(dull) CD11b+. We mapped a locus (provisionally designated Mott-1) controlling Mott cell formation that was tightly linked to microsatellite marker loci, D4 Mit70 and D4 Mit48, of autoimmune NZB mice, which is in close proximity to our recently mapped locus Imh-1 for hypergammaglobulinemia. This region contains candidate genes that may be relevant to the aberrant B cell activation and differentiation. We suggest that while the Mott cell by itself is not the effector for autoimmune disease, the genetically determined aberrant maturational process of B1 cells that underlies the pathogenesis of autoimmune disease forms the basis for Mott cell formation in a T cell-dependent manner.

Animals↗