慢性丙型肝炎患者血清ANA、anti-LKM1的检测及其产生机制探讨

目的 观察慢性丙型肝炎(CHC)患者中抗核抗体(ANA)、抗肝肾微粒体抗体(anti-LKM1)的检出情况,并深入探讨其产生机制.方法 通过多因素分析探讨自身抗体产生与年龄、性别、HCV RNA含量、HCV基因型、生化指标及临床特征等指标的关系.结果 360例CHC患者中,ANA阳性率为12.5%(451360),anti-LKMi的阳性率为2.5%(91360).CHC患者的自身抗体检出率高于慢性乙型肝炎(CHB)患者(15%vs2.9%,P=0.006)而低于自身免疫性肝炎(AIH)患者(15%vs47.9%,P<0.001);女性患者的自身抗体检出率高于男性(P<0.05);自身抗体阳性组HCV RNA含量低于自身抗体阴性组(1.23×107 vs 7.2× 107拷贝/L,P<0.05).自身抗体阳性组和阴性组患者的年龄、HCV基因型、生化指标、肝硬化发生率的差异均无统计学意义.接受干扰素治疗组和未接受干扰紊治疗组患者的自身抗体检出率差异无统计学意义(P>0.05).结论 CHC患者血清中可检测出AIH相关自身抗体;自身抗体可能并非由干扰素治疗所诱发;很可能是HCV引发自身免疫,导致自身抗体的出现.     

Autoantibody prevalence in children with liver disease due to chronic hepatitis C virus (HCV) infection

HCV infection and interferon-alpha (IFN-α) therapy have been associated with autoimmunity. To assess whether chronic liver disease (CLD) due to HCV infection or its treatment with IFN-α cause autoimmune manifestations, the prevalence of tissue autoantibodies in 51 children with chronic HCV infection and 84 with other CLD was analysed by standard techniques. Sixty-five percent of patients with chronic HCV infection, 66% with chronic hepatitis B infection and 60% with Wilson's disease were positive for at least one autoantibody. In the 51 subjects with chronic HCV infection (29 treated with IFN-α, 22 untreated), tested on 165 occasions over a median of 9 months (range 5–42 months), autoantibodies to nuclei (ANA), smooth muscle (SMA), gastric parietal cell (GPC) and/or liver kidney microsomal type 1 (LKM-1) were similarly prevalent in treated and untreated patients (90% versus 68%, P = 0.12). Positivity for SMA was present in 67%, GPC in 32%, ANA in 10%, LKM-1 in 8% of cases. Treatment with IFN-α had to be suspended due to transaminase elevation in one SMA-positive, one ANA-positive but in three of four LKM-1-positive patients. Our results show that: (i) autoantibodies are common in viral-induced hepatitis and Wilson's disease; (ii) positivity for SMA, GPC, ANA is part of the natural course of chronic HCV infection, their prevalence being unaffected by IFN-α; and (iii) IFN-α should be used cautiously in the treatment of LKM-1/HCV-positive patients.     

Proteinase 3 and dihydrolipoamide dehydrogenase (E3) are major autoantigens in hepatitis C virus (HCV) infection

Hepatitis C virus (HCV) infection has been found to be strikingly associated with autoimmune phenomena. The aim of the present study was to investigate the presence of various autoantibodies in patients with HCV infection. Anti-neutrophil cytoplamic antibody (ANCA), anti-dihydrolipoamide dehydrogenase (anti-E3), rheumatoid factor (RF), anti-dihydrolipoamide acetyltransferase (anti-E2), anti-SS-A/Ro (60 kD), anti-SS-A/Ro (52 kD), anti-SS-B/La, anti-topoisomerase II (anti-topo II), anti-cardiolipin (aCL), anti-dsDNA, anti-ssDNA, anti-nuclear antibodies (ANA), anti-proteinase 3 (anti-Pr3) and anti-myeloperoxidase (anti-MPO) were determined in sera from 516 patients with HCV infection, 11 with primary biliary cirrhosis (PBC) and 44 healthy controls. Assays employed were indirect immunofluoresence, the particle latex agglutination test, enzyme-linked immunosorbent assay (ELISA) and immunoblotting. ANCA, anti-E3 antibody and RF were positive in 278/516 (55.6%), 276/516 (53.3%) and 288/516 (56%) patients with HCV infection, respectively. Positivity for ANA was present in 15.8%, anti-ssDNA in 15.6%, anti-dsDNA in 8.5%, aCL in 5%, anti-SS-B/La in 4.1%, anti-SS-A/Ro (60 kD) in 3.9%, anti-E2 in 3.3% and anti-SSA/Ro (52 kD) in 1.2%, anti-MPO in 4.8%, anti-Topo II and anti-actinin in 0%. All sera with ANCA showed c-ANCA patterns and contained anti-PR3 specificity. HCV patients with ANCA showed a higher prevalence of skin involvement, anaemia, abnormal liver function and alpha-Fetoprotein (alpha-FP). HCV patients with anti-E3 antibodies showed a higher prevalence of liver cirrhosis, arthritis, abnormal liver function and elevated alpha-FP levels. The prevalence of autoantibodies was not affected by treatment with interferon-alpha (IFN-alpha). In conclusion, autoantibodies are commonly found in patients with HCV infection. There is a high prevalence of anti-E3, ANCA and RF in these patients. Proteinase 3 and E3 are the major target antigens in HCV infection. HCV may be regarded as a possible causative factor in ANCA-related vasculitis.     

Clinical correlates of the “rods and rings” antinuclear antibody pattern

The “rods and rings” (RR) antinuclear antibody (ANA) pattern is believed to be restricted to hepatitis C virus (HCV) infection and related to the treatment. This is a 4-year retrospective study of all patients with RR pattern from the 20?000 serum samples received at the Hospital Universitari de Bellvitge for ANA testing. Two control groups with HCV patients without RR pattern: ANA-positive (n?=?74) and ANA negative (n?=?75) were included. Eighty-seven patients had samples with the RR pattern. Seventy-three were infected with HCV (prevalence of 15% in the HCV population). The RR pattern could not be related to ribavirin treatment, clinical status, biochemistry data, hepatic fibrosis, IL28B genotype, HCV genotype or the presence of autoantibodies related with autoimmune hepatitis. As 14 cases presented other diseases, mainly of autoimmune origin, the presence of RR antibodies may also be explained by alterations in immune regulation caused by autoimmunity or HCV in a particular genetic background.     

Anti-soluble liver antigen (SLA) antibodies in chronic HCV infection

Hepatitis C infection is associated with autoimmune disorders, such as the production of autoantibodies. Anti-LKM1 and anti-LC1, immunomarkers of type 2 autoimmune hepatitis, have been previously associated with a HCV infection. Anti-Soluble-Liver-Antigen autoantibodies (SLA) are specifically associated with type 1 and type 2 autoimmune hepatitis and more closely related to patients who relapse after steroid therapy. The recent molecular cloning of the soluble liver antigen provides the opportunity to develop more specific tests for the detection of antibodies against it. The aim of this work is to characterize anti-soluble-liver autoantibodies in sera from patients chronically infected by HCV. A recombinant cDNA from activated Jurkat cells coding for the full length tRNP(Ser)Sec/SLA antigen was obtained. ELISA, Western Blot and immunoprecipitation tests were developed and used to search for linear and conformational epitopes recognized by anti-SLA antibodies in sera from patients chronically infected by HCV. Anti-soluble liver antigen antibodies were found in sera from 10.4% of HCV-infected patients. The prevalence was significantly increased to 27% when anti-LKM1 was also present. Most anti-SLA reactivity was directed against conformational epitopes on the antigen. The means titers by ELISA were lower than those obtained in type 2 AIH. The result of autoantibody isotyping showed a subclass restriction to IgG1 and also IgG4. This study shows the presence of anti-SLA antibodies in approximately 10% of HCV infected patients. The prevalence of SLA autoantibodies in HCV infected patients increases when LKM1 autoantibodies are also present. The relationship between the prevalence of this characteristic autoimmune hepatitis autoantibody and the implication of an autoimmune phenomenon in the liver injury of patients chronically infected by HCV needs further investigation.     

Rheumatic manifestations of hepatitis C virus infection are associated with autoantibodies but not viremia

BackgroundTo investigate the associations between extrahepatic manifestations, autoantibodies, and viremia in patients with hepatitis C virus (HCV) infection.MethodsThis cross-sectional study recruited patients with HCV infection from the outpatient department of a tertiary medical center in Northern Taiwan between January 2017 and August 2019. Autoantibody profiles and the clinical parameters of HCV infection were evaluated using laboratory tests, and a questionnaire was used to record extrahepatic manifestations. HCV infection status, including inactive HCV infection, active hepatitis, and cirrhosis, was defined according to abdominal ultrasonography findings and alanine transaminase levels.ResultsA total of 77 patients with HCV were recruited, with 19.5% and 16.9% of patients, respectively, presenting with arthritis and dry eyes. Autoantibody screening revealed rheumatoid factor (RF), antinuclear antibody (ANA), anti-Ro antibody, and anti-La antibody positivity in 20.8%, 23.4%, 13.0%, and 2.6% of the patients, respectively. The presence of RF was associated with arthritis, whereas the presence of ANA was associated with dry eyes but not dry mouth. Active hepatitis and HCV-related cirrhosis were associated with viremia, but not autoantibody profiles.ConclusionIn this single-center study, the prevalence of extrahepatic manifestations and autoantibodies did not differ in patients stratified by the HCV infection status. Rheumatic manifestations were associated with the presence of autoantibodies but not with viremia.     

Organ and non-organ specific autoantibody titres and IgG levels as markers of disease activity: a longitudinal study in childhood autoimmune liver disease

No longitudinal study has investigated whether autoantibody titres and serum IgG levels correlate with disease activity in autoimmune liver disease. To determine this, we investigated prospectively 19 patients on 254 occasions between 10 months to 5 years from diagnosis. Nine had anti-nuclear and/or anti-smooth muscle antibody (ANA/SMA) positive autoimmune hepatitis (type 1 AIH), 5 liver kidney microsomal type 1 (LKM-1) positive AIH (type 2 AIH) and 5 ANA/SMA positive autoimmune sclerosing cholangitis (ASC). Correlation between IgG levels, titres of ANA, SMA and LKM-1 and levels of the organ specific autoantibodies anti-liver specific protein (anti-LSP), and anti-asialoglycoprotein receptor (anti-ASGPR) with biochemical evidence of disease activity, as measured by serum aspartate amino transferase (AST) levels, was sought during the course of the disease. AST levels correlated with levels of anti-LSP, anti-ASGPR and IgG in type 1 and 2 AIH, but not in ASC. Positive correlation with AST was also observed for LKM-1 titres in type 2 AIH and for SMA titres in type 1 AIH, but not in ASC. In both AIH and ASC, AST levels correlated with the T cell-dependent immune responses anti rubella IgG and anti tetanus toxoid IgG, but not with the T cell-independent IgG2 response to pneumococcal capsular polysaccaride. Our results indicate that measurement of organ and non-organ specific autoantibodies and IgG levels may be used to monitor disease activity in AIH.     

Mixed cryoglobulinaemia and chronic hepatitis C virus infection: the rheumatic manifestations.

The prevalence of rheumatologic symptoms in patients with mixed cryoglobulinaemia associated to chronic hepatitis C virus (HCV) infection was investigated. One hundred fourteen patients (96 female, mean age 63.5 years) with chronic HCV infection and cryoglobulinaemia were recruited. The presence, concentration, and type of cryoglobulins were tested by immunofixation. Rheumatoid factor (RF) and antinuclear antibody (ANA) were also measured. Rheumatological related symptoms were investigated by anamnesis and clinical evaluation. HCV genotype was determined by polymerase chain reaction (PCR) with genotype specific primer. Type II cryoglobulinaemia was identified in 39 cases and it was of type III in 58. HCV-RNA genotype was determined in 62 patients: 47 (76%) were infected by genotype1b, 8 (13%) by genotype 2a, while other genotypes were less common. RF and ANA were, respectively, present in 36 (31.5 %) and 4 (3.5 %) patients at low titre (RF < 50 UI/ml, ANA < 1:80). Of the 114 patients, 51 (44.7%) complained for rheumatological symptoms. The mean cryocrit value in these patients was 2,6 %, while in patients with HCV infection, liver disease, and cryoglobulinaemia without rheumatological symptoms the cryocrit value was lower than 0.5% in 50% of cases. It is concluded that patients with chronic HCV infection reported a wide variety of rheumatological manifestations, impairing their quality of life, with discrete frequency. These results suggest that HCV infection should be considered in the differential diagnosis of rheumatological symptoms of unknown origin.     

Anti-Soluble Liver Antigen (SLA) Antibodies in Chronic HCV Infection

Hepatitis C infection is associated with autoimmune disorders, such as the production of autoantibodies. Anti-LKM1 and anti-LC1, immunomarkers of type 2 autoimmune hepatitis, have been previously associated with a HCV infection. Anti-Soluble-Liver-Antigen autoantibodies (SLA) are specifically associated with type 1 and type 2 autoimmune hepatitis and more closely related to patients who relapse after steroid therapy. The recent molecular cloning of the soluble liver antigen provides the opportunity to develop more specific tests for the detection of antibodies against it. The aim of this work is to characterize anti-soluble-liver autoantibodies in sera from patients chronically infected by HCV. A recombinant cDNA from activated Jurkat cells coding for the full length tRNP^(Ser)Sec/SLA antigen was obtained. ELISA, Western Blot and immunoprecipitation tests were developed and used to search for linear and conformational epitopes recognized by anti-SLA antibodies in sera from patients chronically infected by HCV. Anti-soluble liver antigen antibodies were found in sera from 10.4% of HCV-infected patients. The prevalence was significantly increased to 27% when anti-LKM1 was also present. Most anti-SLA reactivity was directed against conformational epitopes on the antigen. The means titers by ELISA were lower than those obtained in type 2 AIH. The result of autoantibody isotyping showed a subclass restriction to IgG1 and also IgG4. This study shows the presence of anti-SLA antibodies in approximately 10% of HCV infected patients. The prevalence of SLA autoantibodies in HCV infected patients increases when LKM1 autoantibodies are also present. The relationship between the prevalence of this characteristic autoimmune hepatitis autoantibody and the implication of an autoimmune phenomenon in the liver injury of patients chronically infected by HCV needs further investigation.     

Organ and Non-organ Specific Autoantibody Titres and IgG Levels as Markers of Disease Activity: A Longitudinal Study in Childhood Autoimmune Liver Disease

No longitudinal study has investigated whether autoantibody titres and serum IgG levels correlate with disease activity in autoimmune liver disease. To determine this, we investigated prospectively 19 patients on 254 occasions between 10 months to 5 years from diagnosis. Nine had anti-nuclear and/or anti-smooth muscle antibody (ANA/SMA) positive autoimmune hepatitis (type 1 AIH), 5 liver kidney microsomal type 1 (LKM-1) positive AIH (type 2 AIH) and 5 ANA/SMA positive autoimmune sclerosing cholangitis (ASC). Correlation between IgG levels, titres of ANA, SMA and LKM-1 and levels of the organ specific autoantibodies anti-liver specific protein (anti-LSP), and anti-asialoglycoprotein receptor (anti-ASGPR) with biochemical evidence of disease activity, as measured by serum aspartate amino transferase (AST) levels, was sought during the course of the disease. AST levels correlated with levels of anti-LSP, anti-ASGPR and IgG in type 1 and 2 AIH, but not in ASC. Positive correlation with AST was also observed for LKM-1 titres in type 2 AIH and for SMA titres in type 1 AIH, but not in ASC. In both AIH and ASC, AST levels correlated with the T cell-dependent immune responses anti rubella IgG and anti tetanus toxoid IgG, but not with the T cell-independent IgG 2 response to pneumococcal capsular polysaccaride. Our results indicate that measurement of organ and non-organ specific autoantibodies and IgG levels may be used to monitor disease activity in AIH.     

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.     

Type 1 diabetes associated and tissue transglutaminase autoantibodies in patients without type 1 diabetes and coeliac disease with confirmed viral infections

Coeliac disease and type 1 diabetes are autoimmune diseases that may share the same initiating environmental factors. In this study, the occurrence of type 1 diabetes associated autoantibodies (GADA and IA-2A) and tissue transglutaminase autoantibodies (TGA) was determined in patients with confirmed viral infections and no signs of type 1 diabetes or coeliac disease. Serum samples from 82 Cuban patients tested positive for PCR and IgG specific to enterovirus (HEV, serotype echovirus 16, 20 samples), Epstein-Barr virus (EBV, 20 samples), cytomegalovirus (CMV, 21 samples), and hepatitis C virus (HCV, 21 samples); and sera from 164 controls negative serologically to EBV, CMV, HCV, and echovirus 16 were enrolled in the study. All subjects were screened for GADA, IA-2A, and TGA. The prevalence of TGA in patients infected with HEV, EBV, CMV, or HCV was 55% (11/20), 25% (5/20), 9.5% (2/21), and 9.5% (2/21), respectively. GADA and IA-2A were found in 15% (3/20) and 25% (5/20) of patients infected with HEV. None of the patients infected by EBV, CMV, and HCV had GADA or IA-2A. All children infected with HEV who were positive for type 1 diabetes-associated autoantibodies were also TGA-positive. None of the sera from uninfected subjects were positive for GADA, IA-2A or TGA. In conclusion, TGA can develop during infection with HEV, EBV, CMV, or HCV, while the emergence of islet cell related autoantibodies is restricted to HEV infections. The findings suggest that HEV may be a shared environmental factor for the development of islet and gut-related autoimmunity.     

The prevalence of autoantibody and its relationship with genotypes of hepatitis C virus in patients with chronic hepatitis C virus infection

The prevalence of autoantibody in the patients with chronic hepatitis C infection, and the relationship between the autoantibodies and HCV genotypes were investigated in this study. One hundred and eight anti‐HCV positive and 86 anti‐HCV negative patients were included in the study. Anti‐HCV were studied by enzyme immunassay (EIA). HCV RNA was determined by real time polymerase chain reaction (PCR) and HCV genotypes were determined by a reverse‐line blot hybridization. Anti‐nuclear antibodies (ANA), anti‐smooth muscle antibodies (ASMA), Anti‐mitochondrial antibodies (AMA), liver kidney microsomal antibodies (LKM) were detected by indirect immunofluorescence assay. Among patients, 13 (12.03%) of 108 were positive for at least one autoantibody. The positivity was not observed in control group. The most prevalent autoantibody in anti‐HCV positive group was ANA. ANA was positive in six HCV patients with genotype 1. In HCV patients with genotype 1, the frequencies of ANA, ASMA, AMA and LKM1 were six, two, three and one, respectively. In HCV patients with genotype 2, ANA was positive one patient and ASMA, AMA and LKM1 were not detected in HCV patients with genotype 2. In conclusion, the autoantibodies in patients with chronic hepatitis C in the study were low as compared to those reported in previous studies.     

Smooth muscle autoantibodies and autoantigens.

Smooth muscle autoantibody (SMA) was first found in the sera of patients with chronic active hepatitis and subsequently in the sera of patients with other autoimmune liver diseases, viral infections, certain cancers, heroin addicts and female infertility. SMA from patients with chronic active hepatitis reacts with many muscle and 'non-muscle' tissues while SMA from patients with other diseases usually reacts only with smooth muscle. These differences in immunofluorescent staining reactions suggest that SMA is a heterogeneous group of autoantibodies reactive with different smooth muscle autoantigens. As further evidence for this are findings that broad-reacting SMA can be absorbed out by actin, whereas autoantibodies reactive only with smooth muscle cannot, and that different SMAs give different immunofluorescent staining patterns using fibroblasts in tissue culture. Such staining patterns correspond to reactivity with either microfilaments, microtubules or intermediate filaments, ubiquitous cytoplasmic structures which make up the 'cytoskeleton'. Autoantibodies to actin-like microfilaments appear specific for chronic active hepatitis, autoantibodies to microtubules occur in infectious mononucleosis whereas autoantibodies to intermediate filaments occur in infectious hepatitis, chickenpox, measles and mumps. Predictably, future studies will show that presence of SMA with specificities for other proteins in the three types of cytoplasmic filaments, and given more information on antigenicity of the proteins and pathogenicity of the corresponding autoantibodies.     

Diagnostic specificity of autoantibodies. II. Clustering of autoantibodies--role in diagnosis and in comparison to E--and EAC-RFC peripheral blood profiles and immunoglobulin levels.

Clustering of ANA and SMA was evaluated in patients with various internal diseases as a pattern of autoantibody formation. SMA was found in ANA positive patients with chronic hepatitis, undefined collagenoses and autoallergic thyroid diseases significantly more frequently, than in patients without any autoallergic disorders. The incidence of SMA in ANA positive cases with SLE and RA did not exceed their predictable by chance incidence. It was not found that clustering of autoantibodies is correlated with the E and C lymphocyte receptor abnormality as compared to the control group. The lowest count of E-RFC was found in SLE cases which differed significantly in this respect from the control group and also from chronic vasculitis cases. The clustering of autoantibodies is not correlated with hyperimmunoglobulinemia.     

Detection and characterization of liver membrane autoantibodies in chronic active hepatitis by a solid-phase radioimmunoassay.

A solid-phase radioimmunoassay was developed to detect antibodies to liver membrane antigens in sera of patients with HBsAg-negative and -positive liver diseases and primary non-hepatic autoimmune diseases. Ten of fourteen patients with HBsAg-negative CAH had autoantibodies detected by RIA; negative results were obtained with sera of seven patients with HBsAg-positive acute and chronic liver diseases, six patients with miscellaneous liver diseases, including two patients with PBC, two healthy blood donors and seven patients with primary non-hepatic autoimmune diseases. Antibodies detected by RIA correlated with liver membrane autoantibodies (LMA) found by indirect immunofluorescence; no correlation was observed with AMA, ANA and SMA. Species-cross-reacting antibodies could be absorbed by preincubation with isolated plasma cell membranes prepared from rabbit livers. Liver membrane autoantibodies detected by RIA were directed against three different antigen fractions obtained from Sepharose 6B chromatography including LSP and LM-Ag. Only three of ten antibodies were directed against species-specific determinants; others cross-reacted with rabbit antigens. Only the antibody to LSP was organ-specific, all others cross-reacted with kidney proteins. Ferritin, human serum albumin and human plasma lipoprotein were excluded as target antigens. Although several sera reacted with identical molecules a remarkable heterogeneity of liver membrane autoantibodies was observed.     

Autoantibody disturbances in affective disorders: a function of age and gender?

BACKGROUND: Numerous investigators have reported increased autoantibodies to a wide variety of native antigens in patients with affective disorders. However, association of autoimmunity with affective subtypes, mood state, psychotropic medications, age, and gender has not been extensively explored. METHODS: The present study assessed 79 bipolar I, 24 bipolar II, and 46 unipolar major depression patients along with 22 healthy, nonpsychiatric controls for the presence of serum antinuclear (ANA), anti-double stranded DNA, antithyroid microsomal, antithyroglobulin, anticardiolipin (ACA) IgM, and ACA IgG antibodies. RESULTS: Consistent with their higher prevalence of autoimmune disease, women exhibited increased levels of ANA and ACA IgM compared to men. ACA IgG antibody titers also increased significantly with age. Contrary to prior reports of general, overall increases in autoantibodies and specific increases in ANA and antithyroid antibodies in depressed patients, we did not see a significant association between any of the autoantibodies and affective subtype, mood state, or psychotropic medications. LIMITATIONS: Affective subgroups were heterogeneous with respect to psychotropic medications, affective state, age, and gender in this retrospective analysis. Subgroup sample size was insufficient to determine whether interactions of these clinical variables may have influenced results. CONCLUSION: These results suggest that gender and age may have more influence on autoantibodies than affective diagnosis, affective state, or medications.     

Mimicry between the hepatitis C virus polyprotein and antigenic targets of nuclear and smooth muscle antibodies in chronic hepatitis C virus infection

Autoantibodies to smooth muscle (SMA) and nuclear components (ANA) arise in the natural course of chronic infection with hepatitis C virus. In view of the growing evidence for 'molecular mimicry' as a mechanism of autoimmunity we investigated whether cross-reactive immune reactions between host smooth muscle/nuclear components and HCV antigens may contribute to the formation of SMA and ANA in chronic HCV infection. Computer-assisted protein database search methods were used to identify three smooth muscle (smoothelin698-717, myosin1035-1054, vimentin69-88) and three nuclear (matrin722-741, histone H2A11-30, replication protein A133-152) host antigens with the highest local sequence similarity to the HCV polyprotein and 20-mer peptides corresponding to these regions were constructed. Sera from 51 children with chronic HCV infection [median age: 8 (2-16); 27 boys], 26 SMA positive and five ANA positive, were tested for reactivity to the synthesized HCV peptides and their human homologues by enzyme linked immunosorbent assay (ELISA). Sera from patients with HBV infection and chronic liver disease of different aetiologies were used as controls. 'Double reactivity' to HCV peptides and smooth muscle/nuclear homologues was associated strongly with HCV infection (P < 0.001 for both). Humoral cross-reactivity was established as the basis for double recognition by competition ELISA. Double-reactivity to smooth muscle and HCV peptide antigens correlated with SMA positivity by indirect immunofluouresence (P = 0.05). Of 15 patients double-reactive to myosin1035-1054 and its HCV homologue, 13 recognized whole myosin by immunoblot. These results suggest that ANA and SMA in chronic HCV infection may arise, at least in part, as a consequence of cross-reactive immune responses to HCV and host smooth muscle/nuclear antigens.     

Clinical significance of autoantibodies in autoimmune hepatitis

The accurate diagnosis and classification of autoimmune hepatitis (AIH) rely upon the detection of characteristic autoantibodies. Positivity for anti-nuclear (ANA) and/or anti-smooth muscle (SMA) autoantibodies defines AIH type 1 (AIH-1), whereas anti-liver kidney microsomal type 1 (anti-LKM1) and/or anti-liver cytosol type 1 (anti-LC1) define AIH type 2 (AIH-2). ANA and SMA, and less commonly anti-LKM1, have also been detected in de-novo autoimmune hepatitis developing after liver transplantation, a condition that may affect patients transplanted for non-autoimmune liver disease. The diagnostic autoantibodies associated with AIH-1 are also detected in the paediatric AIH/sclerosing cholangitis overlap syndrome, referred to as autoimmune sclerosing cholangitis (ASC). ASC, like adult primary sclerosing cholangitis, is often associated with atypical perinuclear anti-neutrophil cytoplasmic autoantibodies (p-ANCA), although p-ANCA are also detected in other autoimmune liver diseases. These associations highlight the necessity for simple and prompt diagnostic autoantibody testing, and the requirement for the accurate interpretation of the results of the tests in the clinical context. Fine-mapping of antigenic autoantibody targets has facilitated the development of rapid molecular assays that have the potential to revolutionise the field if properly standardised and when used in combination with classical immunofluorescence. Despite their diagnostic significance, the pathogenic role of the various autoantibodies and the mechanisms by which they can potentially inflict damage onto the liver cell remain a topic for further research.     

严重急性呼吸综合征自身免疫指标的初步研究

目的　探讨严重急性呼吸综合征(SARS)患者是否存在着自身免疫现象,寻找患者体内异常出现的抗自身组织器官的抗体。方法　随机选取2 7例SARS患者及18例健康献血员对照血清同时应用免疫荧光法检测抗核抗体(ANA)、抗平滑肌抗体(SMA)、抗线粒体抗体(AMA)、抗胃壁细胞抗体(PCA)、抗心肌抗体(HRA) ,应用酶联免疫吸附试验(ELISA)检测抗肝肾微粒体抗体(LKM)及抗线粒体M2亚型抗体,同时利用猴肺组织基质片应用免疫荧光法定位血清中的SARS相关抗体的靶细胞。结果　2 7例SARS患者中有3例ANA阳性、1例SMA阳性、1例AMA阳性、1例LKM阳性、其余均为阴性;18例献血员中有1例ANA阳性、1例AMA阳性,其余均为阴性。统计分析表明SARS患者与献血员间各项自身抗体阳性率差异均不具有统计学意义。在2 7例SARS患者血清中有2 6例在肺组织细小支气管柱状上皮细胞的腔面尖端呈现强阳性荧光信号,献血员中有5例,统计分析表明两者阳性率差异有统计学意义。结论　SARS患者未出现抗肺外组织、器官的自身抗体。患者血清中出现了抗肺组织的自身抗体,定位于细小支气管柱状上皮细胞。