Anti-mitochondrial Research Articles

Peculiarity of Autoimmune Hepatitis Triggered by SARS-CoV-2 Infection.

Recently, medical interest has been growing in SARS-CoV-2 infection and its multiorgan involvement, including the liver. Up until now, a few reports have described autoimmune hepatitis (AIH) triggered by SARS-CoV-2 infection, but no data are available about the specific liver inflammatory infiltrate and cluster of differentiation. We report a case of AIH triggered by SARS-CoV-2 infection, with a particular focus on its histological and mainly immunohistochemical features. A 60-year-old man, with a history of paucisymptomatic SARS-CoV-2 infection that occurred one month earlier, was admitted for alterations of hepatocellular necrosis and cholestasis indexes. He completed vaccination for SARS-CoV-2 a year earlier. The serologies for hepatotropic viruses were negative. The anti- smooth muscle antibodies (ASMA) and antinuclear antibodies (ANA) results were positive. Anti-liver kidney microsome (anti-LKM) antibodies and antimitochondrial (AMA) were negative. By liver biopsy, haematoxylin-eosin staining highlighted severe portal inflammation with a rich CD38+ plasma cell component, while immunohistochemical staining showed low cell CD4+ count and prevalence of CD8+ and CD3+. After biopsy, the patient started an immunosuppressant regimen, with benefit. We can conclude that the patient developed a type 1 AIH triggered by SARS-CoV-2 infection. The presence of CD8 T-cells at immunohistochemical examination suggests different mechanisms from classic AIH. Similar cases are described after AIH triggered by SARS-CoV-2 vaccination. The AIH after SARS-CoV-2 infection developed by the patient showed a histological picture similar to a classic AIH for the abundant presence of plasma cells, and immunohistochemical features similar to those described after SARS-CoV-2-vaccination. Recently, medical interest has been growing in SARS-CoV-2 infection and its multiorgan involvement, including the liver. Underlying mechanisms are not still clear, more likely consisting of an inflammatory and immune mediated process rather than a direct cytopathic damage.Our report describes a rare case of type 1 AIH triggered by SARS-CoV-2 infection, showing a peculiar histological pattern, different from classic AIH, conversely similar to AIH triggered by SARS-CoV-2 vaccination.The mechanisms underlying liver involvement in SARS-CoV-2 infection are still under investigation. Further studies should be encouraged to improve understanding on this focus and to support physicians in its management.

Prevalence and Outcome of Serum Autoantibodies in Chronic Hepatitis C Patients Undergoing Direct-Acting Antiviral Treatment.

BackgroundChronic immune stimulation by hepatitis C virus (HCV) may cause occurrence of several autoantibodies in infected patients, with or without features of clinically overt autoimmune diseases. The recent introduction of direct-acting antivirals (DAAs) has dramatically changed the natural history of chronic HCV infection. The aim of this study was to assess the effects of DAA therapy on serum autoantibodies in chronic hepatitis C (CHC) patients.MethodsThe medical records of 113 CHC patients were reviewed to assess autoantibody behavior following DAA-directed HCV eradication. Statistical analysis was performed to assess correlations between DAA treatment and autoantibody titers, HCV genotypes, and viral loads.ResultsAnti-nuclear (ANA), anti-smooth muscle cell (ASMA) and anti-mitochondrial (AMA) antibody testing was available in 77 patients; 31 out of 77 patients (40%) had one or more serum autoantibodies prior to treatment. Measurement of autoantibody titers before and after HCV eradication was performed in 20 of 31 patients. DAA treatment significantly affected ANA and ASMA titers, leading to disappearance or reduction of autoantibody titers; conversely, AMA were not influenced by DAA treatment. No correlations were observed between autoantibody specificity and both HCV genotypes and viral loads at baseline. Likewise, serum autoantibody titers were independent of HCV genotypes.ConclusionsDAA-directed HCV clearance may interrupt chronic immune stimulation by removing the drive for autoantibody induction. The isolated persistence of autoantibodies in the small fraction of patients who did not show clearance following DAA treatment may require long-term vigilance.

P-29 CLINICAL FEATURES OF PRIMARY BILIARY CHOLANGITIS IN BRAZIL

Little is known about primary biliary cholangitis (PBC) in Latin America, where this disease is thought to be rare. To analyze clinical and biochemical features of Brazilian PBC patients. The Brazilian Cholestasis Study Group multicentre database was reviewed to assess demographics, clinical and laboratory features from PBC patients. 562 patients with PBC were included; 80 (14.2%) had overlapping syndrome with autoimmune hepatitis and were excluded. Most subjects were middle-aged women (95%; mean age 51 ± 11 years) with classical symptoms of pruritus and/or fatigue (65%) and jaundice (22%). Mean time to diagnosis was 2.5 years. Prevalence of antimitochondrial (AMA) and antinuclear antibodies was 82.8% and 72.1%, respectively. Concurrent autoimmune diseases occurred in 18.9%, mainly Hashimoto's thyroiditis and Sjogren syndrome. Celiac disease was diagnosed in 1:80 (1.2%). Osteopenia and osteoporosis were demonstrated in 42% and 26%, respectively. Liver pathology at diagnosis was available for 326 patients (67.6%). One third of them had advanced PBC. After a mean follow-up of 6.2 ± 5.3 years, 32% of the subjects had clinical, laboratory or imaging evidence of cirrhosis. Requirement for liver transplantation and liver-related deaths were reported in 6.6% and 3.2% of the patients, respectively. Hepatocarcinoma was diagnosed in 1.9% of the subjects. A higher predominance of PBC among females, compared to other populations, was observed, while AMA positivity was lower. Concurrent autoimmune, celiac and bone diseases are common and should be adequately screened. Prolonged time to diagnosis and high prevalence of advanced liver disease might reflect difficulties in health care access in Brazil.

Non-organ-specific autoimmunity in adult 47,XXY Klinefelter patients and higher-grade X-chromosome aneuploidies.

Current literature regarding systemic autoimmune diseases in X-chromosome aneuploidies is scarce and limited to case reports. Our aim was to evaluate the frequency of anti-nuclear (ANAs), extractable nuclear (ENA), anti-double-stranded DNA (dsDNAs), anti-smooth muscle (ASMAs) and anti-mitochondrial (AMAs) antibodies in a large cohort of adults with Klinefelter's syndrome (KS, 47,XXY) and rare higher-grade sex chromosome aneuploidies (HGAs) for the first time. Sera from 138 X-chromosome aneuploid patients [124 adult patients with 47,XXY KS and 14 patients with HGA (six children, eight adults)] and 50 age-matched 46,XY controls were recruited from the Sapienza University of Rome (2007-17) and tested for ANAs, ENAs, anti-dsDNAs, ASMAs and AMAs. Non-organ-specific immunoreactivity was found to be significantly higher in patients with 47,XXY KS (14%) than in the controls (2%, p=0.002). Among all the antibodies investigated, only ANAs were observed significantly more frequently in patients with 47,XXY KS (12.1%) than in the controls (2%, p=0.004). No anti-dsDNA immunoreactivity was found. Stratifying by testosterone replacement therapy (TRT), non-organ-specific autoantibody frequencies were higher in TRT-naive (p=0.01) and TRT-treated groups than in controls. No patients with HGA were found positive for the various autoantibodies. Non-organ-specific autoantibodies were significantly present in 47,XXY adult patients. Conversely, HGAs did not appear to be target of non-organ-specific immunoreactivity, suggesting that KS and HGAs should be considered as two distinct conditions. The classification and diagnosis of systemic autoimmune diseases is frequently difficult. To support a correct clinical evaluation of KS disease and to prevent eventual secondary irreversible immune-mediated damages, we highlight the importance of screening for non-organ-specific autoimmunity in Klinefelter's syndrome.

Primary biliary cholangitis with normal alkaline phosphatase: A neglected clinical entity challenging current guidelines

Background & aimThe diagnosis of primary biliary cholangitis (PBC), an uncommon immune-mediated cholestatic liver disease, is based on positive circulating anti-mitochondrial (AMA) and/or PBC-specific anti-nuclear autoantibodies (ANA), coupled with elevated serum alkaline phopsphatase (ALP) levels. Timely initiation of treatment with ursodeoxycholic acid prevents progression to cirrhosis and liver failure. We aimed at investigating liver histology in patients with normal ALP level and positive AMA and/or PBC-specific ANA. MethodsWe searched the Swiss PBC Cohort Study database, which includes subjects with positive PBC autoimmune serology and normal ALP levels, for patients who underwent a liver biopsy. Histological slides were centrally reviewed by an expert liver pathologist, and sera were centrally re-tested for AMA and ANA. Results30 patients were included; 90% females, median age 53 (range 27–72) years. Twenty-four (80%) had liver histology typical for (n = 2), consistent with (n = 16) or suggestive of (n = 6) PBC, including three of four AMA-negative ANA-positive patients. Among 22 ursodeoxycholic acid treated patients, 14 had elevated GGT levels before treatment; a significant decrease of the median GGT level between pre- (1.46 x ULN) and post- (0.43 x ULN) treatment (p = 0.0018) was observed. ConclusionsIn our series, a high proportion of AMA positive patients with normal ALP levels have PBC. For the first time we show histological diagnosis of PBC in AMA-negative/PBC-specific ANA-positive subjects and the potential role of GGT as a biomarker in PBC patients with normal baseline ALP levels. Current guidelines for the diagnosis of PBC do not cover the whole extent of PBC presentation, with important clinical implications in terms of timely treatment initiation.

Novel Anti-Hexokinase 1 Antibodies Are Associated With Poor Prognosis in Patients With Primary Biliary Cholangitis.

Antibodies to hexokinase 1 (HK1) and kelch-like 12 (KLHL12) have been identified as potential biomarkers in primary biliary cholangitis (PBC), and this study assesses changes of these antibodies over time and if they are associated with clinical outcomes. Two hundred fifty-four PBC patients (93.3% female, 51 ± 12.3 years old) were tested for anti-HK1 and anti-KLHL12, antimitochondrial (AMA), anti-gp210, and anti-sp100 antibodies. One hundred sixty-nine patients were tested twice and 49 three times within 4.2 (0.8-10.0) years. Biochemistry and clinical features at diagnosis, response to therapy, events of decompensation, and liver-related death or transplantation were evaluated. Anti-HK1 and anti-KLHL2 were detected in 46.1% and 22.8% patients, respectively. AMA were positive in 93.7%, anti-sp100 in 26.4%, and anti-gp210 in 21.3% of patients. Anti-HK1 and anti-KLHL12 positivity changed over time in 13.3% and 5.5% of patients, respectively. Anti-HK1 or anti-KLHL12 were present in 37.5% of AMA-negative patients, and in 40% of AMA, anti-gp210, and anti-sp100 negative. No significant differences were observed between those with or without HK1 and KLHL12 antibodies, but transplant-free survival and time to liver decompensation were significantly lower in patients anti-HK1 positive (P = 0.039; P = 0.04) and in those anti-sp100 positive (P = 0.01; P = 0.007). No changes in survival and events of liver decompensation were observed according to the positivity of AMA, anti-KLHL12, or anti-gp210 antibodies. HK1 and KLHL12 antibodies are present in 40% of PBC patients who are seronegative by the conventional PBC-specific antibodies. The novel antibodies remain rather steady during the course of the disease, and HK1 antibodies are associated with unfavourable outcomes.

Organ-specific antibodies in LADA patients for the prediction of insulin dependence

ABSTRACTAim of the study: The aim of the present study was to define the frequency of organ-specific and non-organ-specific autoantibodies in a cohort of Latent Autoimmune Diabetes in Adults (LADA) patients and to test whether multiple antibodies positivity could be a predictor of early insulin dependence. Materials and methods: We enrolled 210 LADA and 210 type 2 diabetes mellitus (T2D) patients. In all subjects anti-islet antigen-2 (IA-2Ab), anti-thyroperoxidase (TPOAb), anti-zinc transporter 8 (ZnT8Ab), anti-nuclear (ANA), anti-parietal cell (APCA), anti-smooth muscle (ASMA), anti-mitochondrial (AMA), anti-liver kidney microsomes (LKM), and anti-reticulin (ARA) circulating antibodies were assessed. Results: The frequency of TPOAb, ZnT8Ab, APCA, and IA-2Ab positivity was, respectively, detected in 40.0%, 32.4%, 24.7%, and 9.5% of LADA patients, whereas their frequency was significantly lower in T2D patients (11.4%, 1.9%, 9.5%, and 0.0%, respectively, p < 0.001). The frequency of ANA was the same in both groups whereas the frequency of ASMA, ARA, AMA, and LKM was very low (range 0.0–3.3%). The presence of TPOAb associated with ZnT8Ab, IA-2Ab, or APCA allows one to predict the progression of disease with a high specificity but low sensibility. Conclusions: LADA patients show an increased frequency of organ- and non-organ-specific antibodies. Consequently, a screening is worthwhile in these patients. The simultaneous presence of TPOAb with ZnT8, IA-2Ab, or APCA may help differentiate clinical phenotypes and predict faster insulin dependence in LADA patients.

Prevalence of antimitochondrial antibodies in autism spectrum subjects

ABSTRACT Objective: Autism is a neurodevelopmental disorder characterized by impairment in verbal and nonverbal communication, repetitive and stereotypic behavior. Dysregulated immune system has a role in the pathogenesis of Autism. This study was designed to measure the prevalence of antimitochondrial (AM) antibodies in a group of autistic children. Methods: AM antibodies subtype 2 (AMA-M2) were evaluated by indirect solid phase enzyme immunoassay in 62 autistic children and 14 age-matched healthy controls. Autistic activity was assessed by using the Childhood Autism Rating Scale. Results: Significantly elevated levels of AMA-M2 were observed in the sera of autistic children (n = 54, 0.221 ± 0.029 IU/ml [mean ± SEM]) compared with healthy controls (n = 14, 0.111 ± 0.010 IU/ml [mean ± SEM], p = 0.0008) and there was no significant difference in patients with moderate to severe autism (p = 0.49). AM antibodies in autistic patients have no correlation with Childhood Autism Rating Scale score. Conclusion: The current study demonstrated significantly high levels of AMA-M2 in autistic subjects when compared with healthy controls. Further large-scale studies are required to dissect any pathogenic role of these antibodies in the development of autism.

Clinical features of patients with primary biliary cirrhosis and anti-SP100 autoantibody positivity

To evaluate the clinical features of patients with primary biliary cirrhosis (PBC) and positive expression of sp100 autoantibody in order to generate a clinical screening profile that may help to increase early diagnosis and timely initiation of therapy. The clinical data of 70 patients who were diagnosed with PBC by liver biopsy between January 2006 to December 2009 at the Second Affiliated Hospital of Kunming Medical University of Hepatobiliary and Pancreatic Medicine were retrospectively collected for analysis. The patients were divided according to expression of anti-sp100: positive patients, n = 12; negative patients, n = 58. The groups were comparatively analyzed for differences in clinical, biochemical, immunological, and histopathological parameters. Normally distributed data was compared by t-test, and non-normally data was compared by rank-sum test. There was no significant difference in age among the sp100-positive and sp100-negative patients (51.6 +/- 9.5 vs. 50.0 +/- 14.7 years, P more than 0.05). The sp100-positive group had significantly more women (80.0% vs. 61.9%, X2 = 0.32, P more than 0.05) and more patients with atypical symptoms (18.2% vs. 13.8%) but the difference of the latter did not reach statistical significance. The sp100-positive group had significantly higher levels of alkaline phosphatase (ALP; 466 vs. 163 U/L, Z = 3.71), gamma-glutamyl-transpeptidase (GGT; 728 vs. 154 U/L, Z = 3.38), and immunoglobulin M (IgM; 4.25 +/- 2.86 vs. 2.81 +/- 2.15, t = 2.06, P less than 0.05). Forty of the total patients tested negative for antimitochondrial (AMA)-M2 antibodies, and eight of those were sp100-positive (20.0%) while 18 were antinuclear (ANA) antibody-positive (45.0%). There were significantly more AMA-M2-negative/ANA-positive patients than sp100-positive patients (P = 0.021). Anti-sp100 expression was not associated with the pathological stage of PBC (R1 = 5.500, P more than 0.05). SP100-positive PBC may show a bias towards the female sex, and may be characterized by enhanced serum levels of ALP, GGT, and IgM. Further clinical differences may manifest as the disease progresses, and changes in autoantibodies' expression and liver function markers should be carefully monitored in follow-up.

A CASE OF OVERLAP SYNDROME OF PRIMARY BILIARY CIRRHOSIS AND AUTOIMMUNE HEPATITIS WITH MARKED ELEVATION OF IgM

A 60-year-old woman was admitted to our hospital because of anorexia and vomiting. Hematology revealed elevated levels of hepatobiliary enzymes and positive results for antinuclear antibody (ANA) and antimitochondrial (AMA) M2 antibody. Immunoglobulin (Ig) G and IgM levels were extremely elevated, 3,379 mg/dl and 4,250 mg/dl, respectively. A diagnosis of primary biliary cirrhosis and autoimmune hepatitis (PBC-AIH) overlap syndrome was made. However, IgM levels as high as the level of 4,250 mg/dl in this case has not been reported previously. This case may be of value in studying elevated IgM levels with PBC-AIH overlap syndrome and relationships to the mechanism of onset.

Autoimmune disease and multiple autoantibodies in 42 patients with RASopathies

The association of RASopathies [Noonan syndrome (NS) and Noonan-related syndromes] and autoimmune disorders has been reported sporadically. However, a concomitant evaluation of autoimmune diseases and an assessment of multiple autoantibodies in a large population of patients with molecularly confirmed RASopathy have not been performed. The clinical and laboratory features were analyzed in 42 RASopathy patients, the majority of whom had NS and five individuals had Noonan-related disorders. The following autoantibodies were measured: Anti-nuclear antibodies, anti-double stranded DNA, anti-SS-A/Ro, anti-SS-B/La, anti-Sm, anti-RNP, anti-Scl-70, anti-Jo-1, anti-ribosomal P, IgG and IgM anticardiolipin (aCL), thyroid, anti-smooth muscle, anti-endomysial (AE), anti-liver cytosolic protein type 1 (LC1), anti-parietal cell (APC), anti-mitochondrial (AM) antibodies, anti-liver-kidney microsome type 1 antibodies (LKM-1), and lupus anticoagulant. Six patients (14%) fulfilled the clinical criteria for autoimmune diseases [systemic lupus erythematous, polyendocrinopathy (autoimmune thyroiditis and celiac disease), primary antiphospholipid syndrome (PAPS), autoimmune hepatitis, vitiligo, and autoimmune thyroiditis]. Autoimmune antibodies were observed in 52% of the patients. Remarkably, three (7%) of the patients had specific gastrointestinal and liver autoantibodies without clinical findings. Autoimmune diseases and autoantibodies were frequently present in patients with RASopathies. Until a final conclusion of the real incidence of autoimmunity in Rasopathy is drawn, the physicians should be alerted to the possibility of this association and the need for a fast diagnosis, proper referral to a specialist and ultimately, adequate treatment.

Immunopathogenesis of primary biliary cirrhosis: an old wives' tale

Primary biliary cirrhosis (PBC) is a cholestatic liver disease characterised by the autoimmune destruction of the small intrahepatic bile ducts. The disease has an unpredictable clinical course, but may progress to fibrosis and cirrhosis. Although medical treatment with urseodeoxycholic acid is largely successful, some patients may progress to liver failure requiring liver transplantation. PBC is characterised by the presence of disease specific anti-mitochondrial (AMA) antibodies, which are pathognomonic for PBC development. The disease demonstrates an overwhelming female preponderance and virtually all women with PBC present in middle age. The reasons for this are unknown; however several environmental and immunological factors may be involved. As the immune systems ages, it become less self tolerant, and mounts a weaker response to pathogens, possibly leading to cross reactivity or molecular mimicry. Some individuals display immunological changes which encourage the development of autoimmune disease. Risk factors implicated in PBC include recurrent urinary tract infection in females, as well as an increased prevalence of reproductive complications. These risk factors may work in concert with and possibly even accelerate, immune system ageing, contributing to PBC development. This review will examine the changes that occur in the immune system with ageing, paying particular attention to those changes which contribute to the development of autoimmune disease with increasing age. The review also discusses risk factors which may account for the increased female predominance of PBC, such as recurrent UTI and oestrogens.

Prevalence of non-organ-specific autoantibodies in a rural community from northeastern Brazil: a population-based study

Non-organ-specific autoantibodies (NOSA) are well-recognized diagnostic markers of autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC), but can also be observed in patients with viral hepatitis as well as in healthy subjects. The aim of this study was to evaluate the prevalence of NOSA in subjects living in a rural community in Brazil and to correlate their occurrence with the presence of liver disease. Seven hundred twenty-five apparently healthy subjects were randomly selected for assessment of antinuclear (ANA), anti-smooth muscle (SMA), antimitochondrial (AMA), anti-liver/kidney microsome type 1, and anti-liver cytosol type 1 antibodies. Subjects with those NOSA were evaluated for the presence of AIH, PBC, and viral hepatitis. Reactivities for all NOSA, SMA, ANA, and AMA were detected, respectively, in 14, 10, 4, and 0.1% of subjects, with a mean titer of 1:40. NOSA-positive subjects were significantly older and more frequently females. No correlation was observed between the occurrence of NOSA and PBC, AIH, or viral hepatitis. The prevalence of NOSA in Brazilians was 14%. They were usually low titer. NOSA were more frequently observed in females and older subjects and their presence was not correlated with the presence of AIH, PBC, or viral hepatitis.

Autoantibodies for gastrointestinal organ-specific autoimmune diseases in rheumatoid arthritis patients and their relatives

Clustering of autoimmune diseases is common and may be due to genetic background and exposition to environmental triggers. The aim is to carry out a laboratory and clinical study of the prevalence of gastrointestinal organ-specific autoantibodies in rheumatoid arthritis (RA) patients and their relatives. Serum samples of 156 RA patients, 200 relatives, and 100 healthy controls were studied for anti-smooth muscle antibody (ASMA), anti-mitochondrial (AMA), anti-parietal cell (APCA), anti-liver-kidney microsome (LKM), and anti-endomysium antibodies (IgA-EmA) by indirect immunofluorescence. A total of eight out of the 156 (5.1%) RA patients were positive for the autoantibodies (ASMA = 1; AMA = 2, APCA = 5). In the relative group, 12/200 (6%) had at least one positive autoantibody (ASMA = 1; AMA = 2, APCA = 7, IgA-EmA = 2). In the control group, two out of the 100 (2%) healthy controls were positive (ASMA = 1, APCA = 1). No statistical difference was found between RA patients, their relatives, and controls in relation to the frequency of autoantibodies evaluated. Although RA patients and their relatives have positivity of AMA, ASMA, and APCA without statistical difference in relation to healthy individuals, the findings may be of value for adequate clinical approach of these subjects.

Significantly higher frequencies of presence of serum autoantibodies in Chinese patients with oral lichen planus

Previous studies have shown the presence of serum anti-nuclear (ANA), anti-smooth muscle (SMA), anti-mitochondrial (AMA), anti-gastric parietal cell (GPCA), anti-thyroglobulin (TGA) and anti-thyroid microsomal autoantibodies (TMA) in small groups of patients with oral lichen planus (OLP). In this study, the serum levels of ANA, SMA, AMA, GPCA, TGA and TMA were measured in a group of 320 Chinese OLP patients and 53 healthy control subjects to assess whether Chinese OLP patients had significantly higher frequencies of serum autoantibodies than healthy control subjects and to assess which risk factors had a significant influence on the possession of a specific serum autoantibody in OLP patients. We found that autoantibodies were present in 195 (60.9%) of the 320 OLP patients. The frequencies of presence of serum ANA (28.1%), GPCA (26.3%), TGA (21.3%) and TMA (24.4%) in OLP patients were significantly higher than those (5.7%, 1.9%, 1.9% and 1.9%, respectively) in healthy control subjects (all P-values were < 0.005). Forty-one (12.8%) OLP patients also had anti-hepatitis C virus antibody (HCVA) in their sera. The multivariate logistic regression found that major erosive OLP (EOLP) [odds ratio (OR) = 1.786], TGA/TMA-positivity (OR = 2.517), and HCVA-positivity (OR = 2.214) were significant risk factors to influence ANA-positivity in OLP patients. Moreover, only major EOLP (OR = 1.879) and ANA-positivity (OR = 2.581) were significant risk factors to influence TGA/TMA-positivity in OLP patients. There are significantly higher frequencies of presence of ANA, GPCA, TGA and TMA in Chinese OLP patients than in healthy control subjects.

Autoantibodies in patients treated for active pulmonary tuberculosis

The genesis of auto-immune antibodies directed against the own tissue antigens of a host may be due to the host's immune response to mycobacteria. The prospective study included 110 patients treated for active pulmonary tuberculosis and the control group of 60 healthy subjects, volontary blood donors. Applying the method of indirect immnunofluorescence and cryostat sections of rat organs and human larynx cancer epithelial cell line (HEp-2 cells), the prescence of the following autoantibodies in the serum of the examined patients was examined: anti,nclear (ANA), anticardiac (ACA), antimitochondrial (AMA), antiparietal (APA), anti smooth muscular (ASMA), antithyroidal (ATA), rheumnatoid factor (RF). These autoantibodies were determined in the course oftreatment and five years later. Low levels of some examined autoantibodies were detected in the serum of a number of the examined patients. No significant difference in the presence of the analysed antibodies was registered between the sexes. In the course of the treatment a reversible hyper-gammaglobulinemia developed, which was at least partially due to the presence of autoantibodies in the patients blood serum. Besides possibly involved mechanisms of molecular mimicry and polyclonal lymphocyte activation, the presence of antinuclear antibodies in the patient's serum is at least partially due to isoniazide treatment. The finding of other autoantibodies is nonspecific and not related to the mycobacterial infection or antituberculosis drug administration.

Autoantibodies in patients with Down Syndrome: Early senescence of the immune system or precocious markers for immunological diseases?

Down syndrome (DS) patients present several immunological disturbances, with high rates of infections, malignancies and autoimmune phenomena. The present study aims to evaluate the prevalence of autoantibodies in children and adolescents with DS that are not usually investigated, and to establish possible clinical and laboratory associations. One hundred and fifty Caucasoid DS patients from southern Brazil (93M, 57F; median age 4 years) and 105 healthy children (58M, 47F; median age 8 years) were evaluated for the presence of anti-mitochondrial (AMA), smooth-muscle (SMA), liver-kidney microsomal (LKM), nuclear (ANA), gastric parietal cell (GPC) and neutrophil cytoplasmic (ANCA) antibodies, by indirect immunofluorescence, and rheumatoid factor (RF), by turbidimetry. Forty-three DS patients (28.6%) showed positivity to at least one autoantibody, in comparison with eight of the controls (7.6%; P < 0.001). RF was detected in 28% of the patients and 6.7% of the controls (P < 0.001). ANCA, SMA and ANA were positive in 0.66% of the patients, while AMA, GPC and LKM were negative in all the samples. Currently, none of the RF positive patients has clinical evidence of rheumatic disease. Data from the present study suggest that the high incidence of positive RF observed in DS patients might be related to the senescence of the immune system or could be an earlier marker of rheumatic diseases in these patients.

Cholestatische Hepatitis bei Situs inversus abdominalis

A 75 year old patient was admitted to hospital due to painless jaundice and fatigue. Patient's history was not remarkable for chronic viral hepatitis, autoimmune hepatitis, hereditary metabolic disorders or a hepatotoxic damage. Laboratory tests revealed significant elevation of the parameters of cholestasis and aminotransferase activity, a significantly elevated titer of both antinuclear (ANA) and antimitochondrial (AMA) antibodies. Abdominal ultrasound and computertomography showed no mechanic cholestasis nor tumorous process but a situs inversus abdominalis of the abdominal parenchymatous organs. Portal and periportal inflammation, consistent with autoimmune hepatitis, was diagnosed histologically after performing laparoscopic liver biopsy. Regarding the significantly elevated cholestatic parameters and the positive AMA-autoantibodies AIH-PBC overlap syndrome was highly probable so medical treatment including both ursodeoxycholic acid and immunosuppressive therapy with corticosteroids and azathioprine was started resulting in a continous downward tendency of liver enzymes and an improvement of the patient's clinical condition. Finding the correct diagnosis and therapy of autoimmune liver disease is not always easy and unproblematic. Regarding its sometimes fatal progression and good response towards medical treatment prompt diagnosis and institution of autoimmune hepatitis--alone or combined as PBC/AIH overlap syndrome--should not be deferred. Laparoscopic liver biopsy should be the method of choice in patients's with situs inversus abdominalis regading the variable anatomy.

Serological and Clinical Comparison of Children and Adults with Anti-Endomysial Antibodies

We compared serological and clinical presentation of 38 adults (5 males, 33 females) and 37 children (15 boys, 22 girls) with anti-endomysial antibodies (AEA).AEA, antinuclear (ANA), anti-parietal (APA), anti-thyroid microsomal (ATMA), anti-thyreoglobulin (ATGA), anti-smooth muscle (SMA) and anti-mitochondrial (AMA) antibodies were detected by IIF. Anti-tissue transglutaminase (tTG), anti-extractable nuclear antigens (ENA) and anti-actin (AAA) antibodies were studied by ELISA. There were no differences in frequency of ANA, APA, ATGA, SMA, AMA and AAA in children and adults. ATMA (p < 0.001) and anti-ENA (p < 0.05) positivity were more frequently found in adults. Anti-Ro/SSA had 7/38 adults and 1/37 children (p < 0.05). Adults had more frequently silent form of celiac disease associated with autoimmune diseases (p < 0.001). We are the first to demonstrate that in spite of no difference in ANA positivity in adults and children, ANA in adults more frequently target ENA, especially Ro/SSA antigen. The reason for this ANA specificity could be the longer gluten exposure in adults.

The development of autoantibodies after allogeneic stem cell transplantation is related with chronic graft-vs-host disease and immune recovery

Chronic graft-vs-host disease (GVHD) has certain similarities with autoimmune diseases and is associated with the development of various autoantibodies in some patients. In this study, we analyzed the occurrence of autoantibodies in 63 patients surviving longer than 3 months after an allogeneic haematopoietic stem cell transplantation (HSCT), with the aim of detecting a possible association between occurrence of autoantibodies and development of chronic GVHD and immune recovery after HSCT. The patients were screened every 3 months for the occurrence of the following autoantibodies: anti-nuclear (ANA), anti-mitochondrial (AMA), anti-smooth muscle (ASMA), anti-cardiolipin (ACLA), anti-liver-kidney microsomal (LKM), anti-DNA, anti-neutrophil cytoplasmatic (ANCA), and anti-thyroid antibodies. Peripheral blood immunophenotyping with anti-CD3, CD4, CD8, CD19, CD20, CD16, and CD56 antibodies was evaluated at the same intervals. Autoantibodies were not found in 18 patients (29%), at least in one screening in 29 patients (46%), and in all screenings in 16 patients (25%). ANA were found in 41 patients (65%), AMA in 4 (6%), ASMA in 4 (6%), ANCA in 7 (11%), ACLA in 1 (2%), anti-thyroid antibodies in 3 (5%), and anti-DNA in 2 (3%). More than one antibody occurred in 16/63 (25%) positive patients. ANA was significantly more frequent in patients with chronic GVHD and, among these, in those with the extensive form. The nucleolar pattern of immunofluorescence of ANA but not its titer was correlated with the extension of chronic GVHD. Patients who developed autoantibodies had higher CD20(+) cell blood counts than negative patients in the third month (p=0.006), ninth month (p=0.061), and twelfth month (p=0.043). We conclude that patients with chronic GVHD, particularly those with an extensive involvement, were likely to develop autoantibodies and have a faster B-cell recovery, suggesting a role of B cells in the pathogenesis of chronic GVHD.