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PubMed1992

Autoimmune syndromes in major histocompatibility complex (MHC) congenic strains of nonobese diabetic (NOD) mice. The NOD MHC is dominant for insulitis and cyclophosphamide-induced diabetes.

The development of autoimmune diabetes in the nonobese diabetic (NOD) mouse is controlled by multiple genes. At least one diabetogenic gene is linked to the major histocompatibility complex (MHC) of the NOD and is most likely represented by the two genes encoding the alpha and beta chains of the unique NOD class II molecule. Three other diabetogenic loci have recently been identified in the NOD mouse and are located on chromosomes 1, 3, and 11. In addition to the autoimmune diabetes which is caused by destruction of the insulin-producing beta cells in the pancreas, other manifestations of autoimmunity are seen in the NOD mouse. These include mononuclear cell inflammation of the submandibular and lacrimal glands, as well as the presence of circulating autoantibodies. To determine the effect of the non-MHC diabetogenic genes on the development of autoimmunity, we constructed the NOD.B10-H-2b (NOD.H-2b) strain, which possesses the non-MHC diabetogenic genes from the NOD mouse, but derives its MHC from the C57BL/10 (B10) strain. The NOD.H-2b strain does not develop insulitis, cyclophosphamide-induced diabetes, or spontaneous diabetes. It does, however, develop extensive lymphocytic infiltrates in the pancreas and the submandibular glands that are primarily composed of Thy 1.2+ T cells and B220+ B cells. In addition, autoantibodies are present in NOD.H-2b mice which recognize the "polar antigen" on the insulin-secreting rat tumor line RINm38. These observations demonstrate that the non-MHC genes in the NOD strain, in the absence of the NOD MHC, significantly contribute to the development of autoimmunity. The contribution of a single dose of the NOD MHC to autoimmunity was assessed with a (NOD x NOD.H-2b)F1 cross. Although only approximately 3% of F1 females developed spontaneous diabetes, approximately 50% of both female and male F1 mice developed insulitis, and 25% of females and 17% of males became diabetic after treatment with cyclophosphamide. These data demonstrate that the MHC-linked diabetogenic genes of the NOD mouse are dominant with decreasing levels of penetrance for the following phenotypes: insulitis greater than cyclophosphamide-induced diabetes greater than spontaneous diabetes.

Animals↗

PubMed1993

Mercury-induced autoreactive anti-class II T cell line protects from experimental autoimmune encephalomyelitis by the bias of CD8+ antiergotypic cells in Lewis rats.

Brown-Norway (BN) rats injected with HgCl2 develop a systemic autoimmune disease associated with a polyclonal B cell activation, due to autoreactive T cells specific for self-class II molecules, while Lewis (LEW) rats injected with HgCl2 do not exhibit autoimmunity and develop a non-antigen-specific, CD8-mediated immunosuppression assessed by a depression of T cell functions, and a protection against experimental autoimmune encephalomyelitis (EAE). Resistance to HgCl2-induced autoimmunity is not due to these suppressor cells since treatment with an anti-CD8 monoclonal antibody (mAb) did not allow autoimmunity to appear. The absence of autoimmunity in this strain could result from the absence of autoreactive T cells, or from quantitative or qualitative differences of these cells between susceptible and resistant strains. In the present study, we show that CD4+ anti-class II T cells are present in HgCl2-injected LEW rats and are as frequent as in BN rats when assessed by limiting dilution analysis. LEW CD4+ autoreactive T cell lines were derived. They proliferated in the presence of normal class II-bearing cells, secreted interleukin 2, and did not induce B cells to produce immunoglobulins. Transfer of one of these lines, LEW Hg A, into normal LEW rats led to the appearance of CD8+ cells responsible for a non-antigen-specific immunosuppression that induced complete protection from EAE. Immunosuppression was abrogated after treatment with an anti-CD8 mAb. In vitro, CD8+ cells from rats injected with the LEW Hg A T cell line proliferated in the presence of activated T cells whatever their origin. We conclude that HgCl2 induces CD4+ autoreactive T cells that proliferate in the presence of class II+ cells in susceptible BN as well as in resistant LEW rats. But while these cells collaborate with B cells to produce autoantibodies in BN rats, they initiate in LEW rats a suppressor circuit involving antiergotypic CD8+ suppressor cells.

Animals↗

PubMed1993

The induction of experimental autoimmune myocarditis in mice lacking CD4 or CD8 molecules [corrected].

Experimental induction of most autoimmune diseases appears to depend on the activation of CD4+ T helper cells, while CD8+ lymphocytes may have a role in disease progression. To study the role of CD4+ and CD8+ T cell subsets in T cell-dependent autoimmunity, mice lacking CD4 or CD8 molecules after gene targeting were injected with cardiac myosin to induce organ specific autoimmune myocarditis. Mice homozygous for the CD8 mutation (CD8-/-) developed significantly more severe disease as compared to CD4+/-CD8+/- controls. Surprisingly, CD4-/- mice developed autoimmune myocarditis with infiltration of TCR alpha beta +CD4-CD8- T cells in the heart tissue and appearance of autoantibodies. These data demonstrate that the lack of CD4+ or CD8+ T cells has no significant influence on the initiation of autoimmune myocarditis. CD4+ and CD8+ cells regulate disease severity and these results may explain the occurrence of autoimmunity in CD4 immunodeficiencies.

Animals↗

PubMed1994

Continuous administration of anti-interleukin 10 antibodies delays onset of autoimmunity in NZB/W F1 mice.

We have previously shown that continuous administration of anti-interleukin 10 (anti-IL-10) antibodies (Abs) to BALB/c mice modifies endogenous levels of autoantibodies, tumor necrosis factor alpha (TNF-alpha), and interferon gamma, three immune mediators known to affect the development of autoimmunity in "lupus-prone" New Zealand black/white (NZB/W)F1 mice. To explore the consequences of IL-10 neutralization in NZB/W F1 mice, animals were injected two to three times per week from birth until 8-10 mo of age with anti-IL-10 Abs or with isotype control Abs. Anti-IL-10 treatment substantially delayed onset of autoimmunity in NZB/W F1 mice as monitored either by overall survival, or by development of proteinuria, glomerulonephritis, or autoantibodies. Survival at 9 mo was increased from 10 to 80% in anti-IL-10-treated mice relative to Ig isotype-treated controls. This protection against autoimmunity appeared to be due to an anti-IL-10-induced upregulation of endogenous TNF-alpha, since anti-IL-10-protected NZB/W F1 mice rapidly developed autoimmunity when neutralizing anti-TNF-alpha Abs were introduced at 30 wk along with the anti-IL-10 treatment. Consistent with the protective role of anti-IL-10 treatment in these experiments, continuous administration of IL-10 from 4 until 38 wk of age accelerated the onset of autoimmunity in NZB/W F1 mice. The same period of continuous IL-10 administration did not appear to be toxic to, or cause development of lupus-like autoimmunity in normal BALB/c mice. These data suggest that IL-10 antagonists may be beneficial in the treatment of human systemic lupus erythematosus.

Animals↗

PubMed1999

Monocyte chemoattractant protein 1-dependent leukocytic infiltrates are responsible for autoimmune disease in MRL-Fas(lpr) mice.

Infiltrating leukocytes may be responsible for autoimmune disease. We hypothesized that the chemokine monocyte chemoattractant protein (MCP)-1 recruits macrophages and T cells into tissues that, in turn, are required for autoimmune disease. Using the MRL-Fas(lpr) strain with spontaneous, fatal autoimmune disease, we constructed MCP-1-deficient MRL-Fas(lpr) mice. In MCP-1-intact MRL-Fas(lpr) mice, macrophages and T cells accumulate at sites (kidney tubules, glomeruli, pulmonary bronchioli, lymph nodes) in proportion to MCP-1 expression. Deleting MCP-1 dramatically reduces macrophage and T cell recruitment but not proliferation, protects from kidney, lung, skin, and lymph node pathology, reduces proteinuria, and prolongs survival. Notably, serum immunoglobulin (Ig) isotypes and kidney Ig/C3 deposits are not diminished in MCP-1-deficient MRL-Fas(lpr) mice, highlighting the requirement for MCP-1-dependent leukocyte recruitment to initiate autoimmune disease. However, MCP-1-deficient mice are not completely protected from leukocytic invasion. T cells surrounding vessels with meager MCP-1 expression remain. In addition, downstream effector cytokines/chemokines are decreased in MCP-1-deficient mice, perhaps reflecting a reduction of cytokine-expressing leukocytes. Thus, MCP-1 promotes MRL-Fas(lpr) autoimmune disease through macrophage and T cell recruitment, amplified by increasing local cytokines/chemokines. We suggest that MCP-1 is a principal therapeutic target with which to combat autoimmune diseases.

Animals↗

PubMed2006

Spontaneous autoimmunity prevented by thymic expression of a single self-antigen.

The expression of self-antigen in the thymus is believed to be responsible for the deletion of autoreactive T lymphocytes, a critical process in the maintenance of unresponsiveness to self. The Autoimmune regulator (Aire) gene, which is defective in the disorder autoimmune polyglandular syndrome type 1, has been shown to promote the thymic expression of self-antigens. A clear link, however, between specific thymic self-antigens and a single autoimmune phenotype in this model has been lacking. We show that autoimmune eye disease in aire-deficient mice develops as a result of loss of thymic expression of a single eye antigen, interphotoreceptor retinoid-binding protein (IRBP). In addition, lack of IRBP expression solely in the thymus, even in the presence of aire expression, is sufficient to trigger spontaneous eye-specific autoimmunity. These results suggest that failure of thymic expression of selective single self-antigens can be sufficient to cause organ-specific autoimmune disease, even in otherwise self-tolerant individuals.

Animals↗

PubMed2002

Smoking as a risk factor for Graves' disease, toxic nodular goiter, and autoimmune hypothyroidism.

To study the association between smoking and thyroid disease (Graves' disease [E05.0], nodular toxic goiter [E05.2], and autoimmune hypothyroidism [E03.9]) in a low-iodine intake area a case-control study was undertaken. A self-administered questionnaire was issued to 864 consecutive patients with hyperthyroidism and 628 patients with autoimmune hypothyroidism treated at five university or regional endocrinologic clinics in Denmark between January 1, 1990 and December 31, 1998. Each respondent was compared to an age- (+/- 5 years) and gender-matched normal control person randomly drawn from the background population. A total of 621 patients with hyperthyroidism (72%) and 411 patients with autoimmune hypothyroidism (66%) responded. Of these, 617 (542 females) and 408 (364 females) could be analyzed, respectively. There was an increased risk of both Graves' disease (odds ratio [OR] = 2.5, 95% confidence interval [CI]: 1.8-3.5), toxic nodular goiter (OR = 1.7, 95% CI: 1.1-2.5), and autoimmune hypothyroidism (OR = 1.5, 95% CI: 1.1-2.1) with ever smoking compared to never smoking in women, but not in men. With the high proportion of ever-smokers among women (56%), the attributable risk of smoking in women was 45% in Graves' disease, 28% in toxic nodular goiter, and 23% in autoimmune hypothyroidism. Ever use of oral contraceptives was associated with a slightly lower risk of Graves' disease in women, but not of toxic nodular goiter or autoimmune hypothyroidism. In conclusion, smoking is a powerful risk factor for thyroid disease, especially in populations with a high smoking frequency. Oral contraceptive use is associated with a slightly lower frequency of Graves' disease.

Adult↗

PubMed2003

Impact of previous thyroid autoimmune diseases on prognosis of patients with well-differentiated thyroid cancer.

Autoimmune phenomena are frequently associated with differentiated thyroid carcinomas. However, the significance of thyroid gland autoimmune aggression on the outcome of these patients is still controversial. To address this issue, we studied 173 patients (123 with papillary and 50 with follicular carcinomas) who underwent surgery complemented by radioiodine ablation and followed up for 0.5-29 (6 +/- 5.76) years. Analysis of the prognostic factors revealed that higher age, male gender, larger nodule size, follicular tumors, presence of metastases at diagnosis, grade of differentiation, and stage correlated positively with the occurrence of death, metastasis and/or recurrence, while the presence of antibodies and the previous history of autoimmune disease correlated negatively with these events. Long distant metastases increased the odds for a lower disease-free rate for patients with papillary (8.366 times) and follicular (7.373 times) carcinoma. However, univariate and multivariate analysis failed to demonstrate that neck node involvement could influence the outcome for patients with well-differentiated thyroid carcinoma. The odds for patients with previous history of thyroid autoimmune disease (p < 0.02) or with thyroid autoantibodies (p < 0.001) to have a worse outcome were lower than for patients with no evidence of autoimmune activity, suggesting that autoimmune activity against the gland may exert a protective effect on the outcome of differentiated thyroid carcinoma patients.

Adenocarcinoma, Follicular↗

PubMedDate not supplied

Virus-induced autoimmunity.

Viral infections in humans commonly result in the transient appearance of a variety of autoantibodies and, in some patients, the development of autoimmune tissue injury and disease. The capacity to cause or exacerbate an autoimmune process is common to many viruses, affecting mainly organs injured by the replicating virus, as demonstrated by several animal models. Viral "footprints" can often be found in patients with autoimmune diseases and include high titers of specific antiviral antibodies, identification of viral (retroviral) sequences, and the presence of alpha-interferons in the serum. Several mechanisms that are not mutually exclusive can account for the pathogenesis of virus-induced autoimmunity. Viruses may modify or release sequestered cellular proteins or affect the host's immune system by direct polyclonal activation of B cells, effects on immunoregulatory cells, and release of lymphokines. The appearance of antiviral antibodies may also be deleterious to the host through molecular mimicry, the generation of anti-idiotypic antibodies, or the formation of immune complexes. No single microorganism or mechanism can explain the extremely varied phenomena of autoimmunity, but growing evidence suggests that certain viral infections may lead to clinically manifest autoimmunity in individuals having genetic and possibly other predisposing factors.

Animals↗

PubMed2005

Reduced semen quality in chronic prostatitis patients that have cellular autoimmune response to prostate antigens.

BACKGROUND: The relationship between chronic prostatitis and fertility has been controversial for many years. We have previously shown the presence of a cellular autoimmune response against prostate antigens in a group of chronic prostatitis patients. Our main goal was to investigate whether chronic prostatitis (either caused by an infection or an autoimmune response to the prostate gland) could have a deleterious effect on semen quality. METHODS: Forty-four patients diagnosed as suffering from chronic prostatitis were included and divided into groups according to the presence of infection and/or cellular autoimmune response against prostate antigens. Healthy normal individuals were included as controls. Measurements for sperm concentration, motility, morphology, prostate and seminal vesicle markers, antisperm antibodies, white blood cells and pro-inflammatory cytokines were performed accordingly. RESULTS: The most severe abnormalities were seen in patients with no evident infection and an autoimmune response against prostate antigens. Moreover, significantly increased levels of pro-inflammatory cytokines were detected in seminal plasma from these patients. CONCLUSIONS: This study shows that chronic prostatitis patients with cellular autoimmune response to prostate antigens present important alterations in their semen quality parameters. We speculate that an autoimmune response against prostate antigens and the inflammatory process involved may affect male fertility.

Adult↗

PubMed2000

Contribution of H-2 and non-H-2 genes in the control of mercury-induced autoimmunity.

Mercury-induced autoimmunity is characterized by a T cell-dependent B cell activation (mainly of IgG1 and IgE isotypes), production of anti-nucleolar autoantibodies (ANolA) and the formation of renal IgG deposits. The autoimmunity is to a large extent controlled by genetic factors. We studied 15 different inbred mouse strains of seven H-2 (mouse MHC) genotypes to determine the importance of H-2 and non-H-2 background genes in mercury-induced autoimmunity. The tested strains exhibited a diverse autoimmune response to mercury. In each H-2 genotype, there was at least one strain which responded to mercury by the production of high levels of IgG1 and IgE Ig as well as by the development of high titers of renal IgG1 deposits. Only mouse strains with H-2(s) and H-2(q) genotypes, irrespective of their background genes, produced ANolA after mercury treatment. Only SJL (H-2(s)) and A.SW (H-2(s)) mice were highly susceptible to all characteristics of mercury-induced autoimmunity. NZB (H-2(d)) mice were also highly susceptible, but they did not develop ANolA. Only the DBA/2 (H-2(d)) strain was found to be resistant to all tested mercury-induced autoimmune manifestations, suggesting that non-responsiveness to mercury in DBA/2 mice was largely influenced by non H-2 genes. These findings imply that H-2 genes mainly determine the susceptibility to mercury-induced ANolA production, whereas non-H-2 genes control the susceptibility to and the severity of the B cell activation and renal IgG deposition.

Animals↗

PubMed2004

Localized scleroderma is an autoimmune disorder.

OBJECTIVES: There have been many studies suggesting that localized scleroderma has a strong autoimmune background, although the lesions are usually limited to the skin and subcutaneous tissue. Here we summarize previous data on the autoimmunity of localized scleroderma, mostly published in the last two decades, because there has not been a review paper summarizing autoimmunity in this disorder. METHODS: We classified the previous reports into three categories: antinuclear antibodies; cytokine and soluble receptors; and cell adhesion molecules and cell surface molecules. In each category, we introduce the important investigations. RESULTS: High frequencies of antinuclear antibodies, detected by the indirect immunofluorescence method using cultured cells, are confirmed by many groups. The major autoantigens have been revealed to be histones. Recently, anti-topoisomerase II alpha antibody has been found to be detected highly frequently in localized scleroderma, while anti-topoisomerase I antibody, which is highly specific for systemic sclerosis, has not been detected in any case of localized scleroderma. In other studies, elevated serum cytokines and cell adhesion molecules suggest the immunoactivation of localized scleroderma. CONCLUSIONS: Many previous studies conclude that localized scleroderma involves autoimmune abnormalities and is one of the organ-specific autoimmune disorders targeting mainly skin, although the types of autoimmune abnormality are different from systemic sclerosis.

Antibodies, Antinuclear↗

PubMed1988

Interferons and autoimmunity.

Autoimmunity can be accelerated in several genetically prone murine models and can even be induced in normal mice by treatment with interferon (IFN) or IFN-inducers. Several cases of IFN-induced autoimmune disease in humans also have been observed; however, more striking is the fact that some of the clinical manifestations in autoimmune diseases and many of the immunological aberrations can be mediated or enhanced by IFN. The finding of high levels of circulating IFN in many patients may be highly significant in that respect, and the characterization of the predominant type of IFN as an unusual acid-labile IFN-alpha may indicate an infectious etiologic agent in autoimmunity, since this peculiar IFN was mostly associated with viral infections in vivo or in vitro. The induction of MHC class II antigens on previously HLA-DR or Ia negative cells appears to be caused primarily by IFN-gamma and may have a central role in the pathogenesis of autoimmunity in susceptible individuals. Such aberrant HLA-DR expression on nonlymphoid cells can be detected early in the disease in the target organs of many varied autoimmune conditions and may trigger a cascade of self-directed, uncontrolled immune response in conjunction with other factors.

Animals↗

PubMed1991

Immunogenetics of autoantibodies and autoimmune diseases.

The genetic contribution to the development of autoimmune disease is most likely complex. Along with loci controlling histocompatibility antigens and T-cell receptor proteins, genes that encode autoreactive immunoglobulins may have an important role in the pathogenesis of rheumatoid arthritis and related autoimmune diseases. Although much previous work in this area has concentrated on human monoclonal paraproteins and autoimmune mouse strains, the studies reviewed here examine immunoglobulin genes in the normal human population and normal mouse strains as well as in patients with autoimmune disease. Taken together, these studies suggest that genetic control of the expression of autoimmunity in rheumatoid arthritis and related autoimmune disorders is complex and most likely involves multiple gene loci.

Arthritis, Rheumatoid↗

PubMed2003

Autoimmune thyroid disease and celiac disease in children.

BACKGROUND: Celiac disease (CD) may be associated with other immunologic disorders in adults and children. Previous studies linking CD and autoimmune thyroid disease in children have included very few patients with limited biochemical and immunologic screening tests. The aim of this multicenter study was to establish the prevalence of autoimmune thyroid involvement in a large series of pediatric patients with CD. METHODS: Five hundred seventy-three consecutive pediatric patients were enrolled from clinics in Torino, Bologna, Foggia, Rome (two clinics), Naples, and Bari. Three hundred forty-three patients with CD were studied, 230 girls and 113 boys (median age, 8.5 years). Two hundred fifty-six of the patients with CD (median age, 9 years) had been following a gluten-free diet for 3 months to 16 years; 87 patients were untreated (median age, 6.2 years). The diagnosis of CD was made using the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) criteria. A control group of 230 subjects (median age, 8.3 years) was enrolled. Serum free triiodothyronine, free thyroxine, and thyroid-stimulating hormone (TSH), antithyroperoxidase, antithyroglobulin, anti-TSH receptor antibodies, and thyroid echographic pattern were considered. RESULTS: Autoimmune thyroid disease was found in 90 of 343 (26.2%) patients with CD (62 on a gluten-free diet) and in 20 (10%) of the control subjects (P = 0.001). Fifty-four (15.7%) patients with CD and autoimmune markers had normal thyroid function (euthyroidism) as did 12 (6.0%) of the control subjects; hypothyroidism was observed in 28 (8.1%) patients with CD and in 7 (3.5%) of the control subjects. Hyperthyroidism was diagnosed in four patients with CD and in none of the control subjects with autoimmune markers. An abnormal echographic pattern was seen in 37 patients with CD (16.8%) and only in 1 (1.6%) of the control subjects (P = 0.002). CONCLUSIONS: The high frequency of autoimmune thyroid disease found among patients with CD, even those on a gluten-free diet, may justify a thyroid status assessment at diagnosis and at follow-up evaluation of children with CD.

Adolescent↗

PubMed2000

Aldosterone (mineralocorticoid) equivalent to prednisolone (glucocorticoid) in reversing hearing loss in MRL/MpJ-Fas1pr autoimmune mice.

HYPOTHESIS: Although the glucocorticoid prednisone is the standard therapy for autoimmune sensorineural hearing loss, what this hormone does in the ear to restore hearing is not known. MRL/MpJ-Fas(lPr) autoimmune mice consistently have shown only stria vascularis disease, implying that abnormal ion balances in the endolymph underlie cochlear dysfunction. Previously we have shown that hearing loss in these mice is reversed with prednisolone treatment. This, coupled with the complete lack of cochlear inflammation, suggests that the restoration of hearing with prednisolone is due to its sodium transport function and not to its anti-inflammatory or immune suppression effects. Therefore the hypothesis of this study was that the mineralocorticoid aldosterone, which only increases sodium transport, would be as effective as prednisolone in reversing autoimmune hearing loss. STUDY DESIGN: MRL/MpJ-Fas(lPr) autoimmune mice were treated with either prednisolone or aldosterone to compare steroid effects on auditory brainstem response (ABR) thresholds and stria morphology. METHODS: After baseline ABR audiometry, autoimmune mice were given prednisolone (5 mg/kg per day), aldosterone (15 microg/kg per day), or water in their drinking bottles. After 2 months of treatment the ABR thresholds were remeasured, and ears collected for histological examination. RESULTS: The untreated controls showed continued elevation of ABR thresholds and edematous stria. However, thresholds in most steroid mice were improved or unchanged and their stria morphology improved, particularly with aldosterone treatment. CONCLUSIONS: Restoration of hearing with steroid treatment is due to increased sodium transport to re-establish cochlear ionic balances. Aldosterone therapy may offer advantages over prednisone for long-term management of not only autoimmune hearing loss, but also other forms of nonimmune-related deafness for which steroids are currently prescribed.

Aldosterone↗

PubMed1998

Outcome of autoimmune hepatitis after liver transplantation.

BACKGROUND: Recurrence of autoimmune hepatitis after liver transplantation is not rare, but there is little information about its time of onset, risk factors, response to treatment and prognosis. The aim of this study was to evaluate the rate of recurrence and outcome of autoimmune hepatitis after transplantation. METHODS: The records of patients transplanted in eight centers in our country between 1984 and 1996 were retrospectively analyzed. RESULTS: Forty-three of the 2331 (1.8%) recipients fulfilled diagnostic criteria of autoimmune hepatitis at the time of transplantation. Sixteen patients were excluded from evaluation. Nine (33%) of the 27 patients evaluated fulfilled criteria for recurrence of autoimmune hepatitis, with a mean time of recurrence after orthotopic liver transplantation of 2.6+/-1.5 years. Patients with recurrence had a longer follow-up time after transplantation (5.1 vs. 2.5 years, P=0.0012) and were receiving less immunosuppressive treatment. The estimated risk of recurrence of autoimmune hepatitis in the graft increased over time: 8% over the first year and 68% 5 years after transplantation. None of the seven patients with liver-kidney microsomal-positive antibodies recurred (P=0.059). Fifty percent of the patients failed to respond or responded only partially to therapy, although none of the patients have deteriorated clinically after 2.4+/-1.06 years of follow-up after recurrence. CONCLUSIONS: Recurrence of autoimmune hepatitis in the graft is a common event with an incidence that increases over time as immunosuppression is reduced. Although response to treatment is poor, patient and graft survival do not appear to be decreased.

Adult↗

PubMed2002

Immunohistochemical differences in the portal tract and acinar infiltrates between primary biliary cirrhosis and autoimmune cholangitis.

BACKGROUND: Antimitochondrial antibody-negative primary biliary cirrhosis, or autoimmune cholangitis, may be indistinguishable clinically and histologically from antimitochondrial antibody-positive primary biliary cirrhosis. AIMS: We aimed to compare the phenotypic markers of the portal and acinar infiltrates in autoimmune cholangitis and antimitochondrial antibody-positive primary biliary cirrhosis. PATIENTS AND METHODS: Formalin-fixed, paraffin-embedded liver sections were identified from 32 patients with a clinical and histological diagnosis of primary biliary cirrhosis. Thirteen were antimitochondrial antibody-negative (autoimmune cholangitis group) and 19 were antimitochondrial antibody-positive. The groups were well matched for age, histological stage, liver biochemistry and drug treatment. Immunohistochemical staining was performed using monoclonal antibodies against CD3 (pan T cell), CD8 (cytotoxic), CD45RO (memory), CD45RA (naive), CD68 (macrophages) and against the secreted form of eosinophilic cationic protein (EG2). RESULTS: In autoimmune cholangitis, both portal and acinar CD3 cell counts were significantly higher than in antimitochondrial antibody-positive primary biliary cirrhosis (median portal count 421 vs 257 cells/graticule, P< 0.03; median acinar count 18 vs 9 cells/graticule, P< 0.02). There were no differences between the groups in portal or lobular CD8, CD45RO, CD45RA, CD68 or EG2. Of the total group (antimitochondrial antibody positives and negatives), there were significantly more CD45RA cells in early (stage 1) compared with cirrhotic (stage 4) disease (median 19.3 vs 14 cells/graticule, P< 0.03). EG2 staining was found in eight of the 32 sections overall, but not in the patients with stage 1 disease (P< 0.04). CONCLUSION: CD3 counts are higher in autoimmune cholangitis than in antimitochondrial antibody-positive primary biliary cirrhosis in both portal and acinar areas. However, there are no significant differences in memory/naïve T-cell subsets between both conditions and, in both, loss of naive T lymphocytes and secretion of eosinophilic cationic protein occur with disease progression. This implies that the effector pathways of bile duct destruction are similar in autoimmune cholangitis and primary biliary cirrhosis.

Antibodies, Monoclonal↗