High prevalence of a variety of autoantibodies in a population of hepatitis C virus‐infected individuals

Hepatitis C virus (HCV) infection has been related to self‐reactivity, extrahepatic manifestations and autoimmune diseases. The main goals of this work were to study the prevalence of autoantibodies and their relationship with viral titers and biochemical markers of hepatic damage in patients infected with HCV. Autoantibodies (ANA, AMA, SMA, APC, LKM, DNAds, ANCA, ATG and RF) were determined in 73 individuals with chronic HCV infection and 44 healthy volunteers. The presence of these antibodies was related to demographic variables, viral titers and biochemical parameters. A high prevalence of autoantibodies, particularly for RF, that was associated with female gender was observed in HCV‐infected patients. In addition, SMA, ANA and ATG showed increased frequencies in HCV infection. Interestingly, the concurrent detection of SMA and more than one autoantibody was associated with high gGT levels. Notably, concurrent higher gGT, HCV and SMA levels were observed in male patients as compared to their female counterparts. These results indicate a relationship between HCV infection and the concurrent detection of various autoantibodies in the absence of symptoms of autoimmune diseases. They also suggest a link among the presence of a variety of autoantibodies simultaneously with SMA, increased gGT levels and HCV titers in a population of male patients.     

Poor performance of hepatitis C antibody tests in hospital patients in Uganda

Most hepatitis C testing in Uganda is performed using commercial rapid strip assays (RSA) to detect antibodies to hepatitis C virus (anti‐HCV), rather than enzyme immunoassays (EIA). The prevalence of hepatitis C antibodies in a Ugandan hospital population was determined using both methods to test their accuracy using nucleic acid testing (NAT) as a reference. Sera from 380 consecutive hospitalized Ugandan patients were tested for anti‐HCV using an RSA in Uganda, with subsequent automated third‐generation EIA testing in the United States, followed by NAT. Recombinant immunoblot assays (RIBA) were used as a supplementary test to detect anti‐HCV epitopes. Overall, anti‐HCV was detected in 48/380 (13%) by one or both antibody tests. Anti‐HCV was detected in 19 (5.0%) patients by RSA and in 33 (8.7%) patients by EIA; only four patients were anti‐HCV positive by both methods. Fourteen of the 48 anti‐HCV positive patients had detectable serum HCV RNA, 7 each by bDNA assay or by PCR. RSA detected only 7 of 14 HCV RNA positive sera. Of 29 RNA negative but anti‐HCV positive patients tested by RIBA, only two were anti‐HCV positive; 27 were anti‐HCV negative or indeterminate. Anti‐HCV testing by RSA and/or EIA was neither sensitive nor specific for detection of ongoing HCV infection in hospitalized Ugandan patients. Our findings underscore the importance of confirmatory nucleic acid testing, which, despite its increased cost, appears essential to manage African patients with HCV. J. Med. Virol. 82:1371–1378, 2010. © 2010 Wiley‐Liss, Inc.     

Frequent detection of hepatitis B virus DNA in hepatocellular carcinoma of patients with sustained virologic response for hepatitis C virus

Hepatocellular carcinoma (HCC) develops several years after the eradication of hepatitis C virus (HCV) by interferon therapy. Risk factors for the development of HCC are only partly understood. To elucidate the role of occult hepatitis B virus (HBV) infection in hepatocarcinogenesis in patients with sustained virologic response, the prevalences of HBV‐related makers were examined. Study group comprised 16 patients with sustained virologic response (group A) and 50 with HCV (group B). Anti‐HBc and anti‐HBs in serum were examined by enzyme‐linked immunoassay. HBV DNA in liver was examined by nested polymerase chain reaction, using primers specific for genes encoding for HBx, HBsAg, HBcAg, and HBV cccDNA. Sequence of the amplified HBV DNA for ‘a’ determinant of HBsAg was determined in HCC. Anti‐HBc was positive in 10 of 16 in group A and 25 of 50 in group B. HBV DNA in liver was detected in 12 of 16 in group A and 21 of 50 in group B (P = 0.044). In group A, HBV DNA in liver was detected frequently in patients without cirrhosis and in those with a longer period from the time of HCV eradication to the development of HCC. Mutation in ‘a’ determinant of HBsAg was found in three HCC of group A. Occult HBV infection may be one of the most important risk factors in hepatocarcinogenesis of Japanese patients with sustained virologic response. J. Med. Virol. 81:1009–1014, 2009. © 2009 Wiley‐Liss, Inc.     

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.     

Hepatitis C virus infection in the family setting of patients with occult hepatitis C

Family members of patients with chronic hepatitis C virus (HCV) infection are at increased risk of HCV infection but the prevalence of HCV among family members of patients with occult HCV infection is not known. Anti‐HCV, serum HCV RNA and levels of liver enzymes were determined in 102 family members of 50 index patients with occult HCV infection and in 118 family members of 59 chronic hepatitis C index patients. HCV RNA and/or anti‐HCV were detected in 10/102 (9.8%) relatives of patients with occult HCV infection and in 4/118 (3.4%) of patients with chronic hepatitis C. Fourteen additional family members (seven were relatives of index patients with occult HCV infection) had abnormal values of liver enzymes without serological markers of HCV infection. Two of these patients (who were relatives of two index patients with occult HCV infection) underwent a liver biopsy and were diagnosed with an occult HCV infection because HCV RNA was detected in the liver cells in the absence of serological HCV markers. In conclusion, the prevalence of HCV infection among family members of patients with occult HCV infection was similar to that found among family members of patients with chronic hepatitis C. This stresses the need to adopt strategies to prevent the transmission of HCV in the family setting of patients with occult HCV infection. J. Med. Virol. 81:1198–1203, 2009. © 2009 Wiley‐Liss, Inc.     

Autoantibodies in Argentine women with recurrent pregnancy loss

PROBLEM: To determine the presence or absence of subclinical autoimmunity in Caucasian Argentine healthy women with first trimester recurrent pregnancy loss (RPL), the sera of 118 healthy women with a history of three or more consecutive abortions and 125 fertile control women without abortions and two children were analyzed for the presence of autoantibodies: immunoglobulin (Ig)G and IgM anticardiolipin, antinuclear (ANA), antismooth muscle (ASMA), antimitocondrial (AMA), antiliver-kidney-microsomal fraction (LKM), antigastric parietal cells (GPC), antineutrophil cytoplasmatic (ANCA) and antibodies antigliadin type IgA and IgG and IgA antitransglutaminase related with celiac disease (CD). METHOD OF STUDY: ANA, ASMA, AMA, anti-LKM, antibodies to GPC and ANCA were determined by indirect immunofluorescence (IFI) and anticardiolipin, antigliadina and antitransglutaminase antibodies were measured by enzyme-linked immunosorbent assays (ELISA). RESULTS: There was no significant difference between controls and patients with ANA, ASMA, AMA, LKM, ANCA and GPC. The prevalence of anticardiolipin antibodies in RPL was significantly higher than controls (P < 0,01) and the prevalence of positive antibodies for antigliadina type IgA and IgG and IgA antitransglutaminase in RPL was significantly higher than controls (P < 0.04). CONCLUSION: We show that Caucasian Argentine women with RPL showed significantly higher incidence of anticardiolipin antibodies than normal controls and finally we recommended the screening of IgA and IgG antigliadina and IgA antitransglutaminase antibodies in pregnancy, because of the high prevalence of subclinical CD in RPL and the chance of reversibility through consumption of a gluten free diet.     

多种自身抗体联合检测对自身免疫性肝病的诊断价值

目的：分析各种肝病患者多种自身抗体的检出率,探讨其对自身免疫性肝病（autoimmune liver diseases,ALD）的诊断价值。方法：根据临床诊断将患者分为ALD组（n=96）、病毒性肝炎组（n=135,包括75例乙型肝炎,65例丙型肝炎）,另取62例健康体检者作为健康对照组（n=62）;其中,ALD组又分为自身免疫性肝炎组（AIH组,n=36）、原发性胆汁性肝硬化组（PBC组,n=58）、原发性硬化性胆管炎组（PSC组,n=2）。用间接免疫荧光法检测上述各组的抗核抗体（antinuclear antibodies,ANA）、抗平滑肌抗体（anti-smooth muscle antibodies,ASMA）、抗线粒体抗体（antimitochondrial ant-ibodies,AMA）;用Western印迹法检测抗肝肾微粒体Ⅰ型抗体（anti liver-kidney microsomal antibody Type 1,LKM-1）和抗线粒体Ⅱ型抗体（subtype of AMA,AMA-M2）、抗可溶性肝抗原/胰抗原抗体（soluble liver antigen/liver pancreas,SLA/LP）、抗肝细胞溶质抗原Ⅰ型抗体（antihepatocyte cytosol antigen Type 1,LC-1）。结果：AIH组ANA阳性率（69.4%）和PBC组ANA阳性率（87.9%）显著高于病毒性肝炎组（37.3%）和健康对照组（4.8%）（均P〈0.01）;AIH组ASMA,LKM-1,SLA/LP,LC-1阳性率（44.4%,11.1%,2.8%,8.3%）显著高于病毒性肝炎组（1.3%,1.7%,0,0）和健康对照组（均P〈0.01）;PBC组AMA-M2阳性率（91.3%）显著高于病毒性肝炎组（1.3%）和健康对照组（0）（均P〈0.01）。结论：联合检测ANA,ASMA,LKM-1,SLA/LP,LC-1和AMA-M2等自身抗体可提高ALD诊断的灵敏性和特异性,且对ALD分型、诊疗具有重要意义。     

Diagnosis of occult hepatitis C without the need for a liver biopsy

The diagnosis of occult hepatitis C virus (HCV) infection is based on the presence of HCV‐RNA in the liver. This study aimed to evaluate the use of combining non‐invasive assays to diagnose occult HCV. A total of 122 patients with occult HCV (HCV‐RNA in the liver without detectable anti‐HCV and serum HCV‐RNA) and 45 patients with cryptogenic chronic hepatitis (without HCV‐RNA in the liver and negative for anti‐HCV and serum HCV‐RNA) were included. HCV‐RNA was tested in peripheral blood mononuclear cells (PBMCs) and in 2 ml of ultracentrifuged serum. Anti‐core HCV was examined by a non‐commercial enzyme‐linked immunosorbent assay. All controls were negative for the three HCV markers studied. Among patients with occult HCV, 36% were anti‐core HCV positive, 57% had serum HCV‐RNA after ultracentrifugation, and 61% had HCV‐RNA in PBMCs. Combining the results of the assays, 91% of the patients were positive for at least one marker. Intrahepatic HCV‐RNA load was significantly higher in patients who were positive simultaneously for the three HCV markers than in patients who were negative for all markers (P = 0.006) and than in those with one or two HCV markers (P = 0.039). Replication of HCV in liver was detected more frequently in patients with three (93%, P = 0.002), two (82%, P = 0.001), and one HCV marker (73%, P = 0.011) than in those without markers (27%). In conclusion, testing for all these markers allows diagnosis of occult HCV without the need for a liver biopsy and these assays may help to elucidate the clinical significance of occult HCV infection. J. Med. Virol. 82:1554–1559, 2010. © 2010 Wiley‐Liss, Inc.     

Molecular analysis of transmission of hepatitis C virus in a nurse who acquired acute hepatitis C after caring for a viremic patient with epistaxis

A 23‐year‐old nurse (HC‐IP) developed acute hepatitis C. Intrafamilial transmission of hepatitis C virus (HCV) was suspected initially because her parents were carriers of HCV of the same genotype (1b) as that of Patient HC‐IP. However, the HCV isolate from Patient HC‐IP and those from her parents shared identities of only 92.4–92.7% in the 1,087‐nucleotide (nt) sequence within the NS5B region. It was then suspected that she contracted HCV infection during medical practice. Sixteen patients with antibodies to HCV (anti‐HCV) were hospitalized 1–3 months before she became positive for anti‐HCV. Upon analysis of stored serum samples, 14 of the 16 patients were found to be positive for HCV RNA, and 9 of the 14 viremic patients had genotype 1b HCV. Although the shared identities between the HCV isolate from Patient HC‐IP and those from eight of the nine patients were merely 90.6–93.9% within the 1,087‐nt NS5B sequence, the HCV isolate from the remaining one patient (HC‐P12) was 99.7% identical to that from Patient HC‐IP. Upon analysis of the E1 and E2 junctional region including hypervariable region 1 (283 nt), there was a close relationship (99.3–100%) between clones obtained from Patients HC‐IP and HC‐P12. Although the nurse HC‐IP had a finger injury, she took care of Patient HC‐P12, a 70‐year‐old man with HCV‐related cirrhosis and recurrent epistaxis, occasionally without wearing protective gloves. This study indicates the occurrence of HCV transmission by exposure of nonintact skin to blood in health care settings. J. Med. Virol. 81:1363–1370, 2009. © 2009 Wiley‐Liss, Inc.     

Prevalence of systemic autoimmune rheumatic diseases and clinical significance of ANA profile: data from a tertiary hospital in Shanghai,China

It is necessary and useful to explore prevalence of various systemic autoimmune rheumatic diseases (SARDs) in patients with suspicion of having SARDs and to characterize antinuclear antibodies (ANA) profile for identifying different populations (SARDs and non‐SARDs). A total of 5024 consecutive patients with available medical records were investigated, whose sera had been tested for ANA profile, including ANA, anti‐dsDNA and anti‐extractable nuclear antigen (ENA) antibodies, between 31 January 2012 and 26 March 2014. Only 594 (11.8%) patients were diagnosed with SARDs of those suspected with SARDs. The prevalence of systemic lupus erythematosus (SLE) was highest (3.2%), followed by rheumatoid arthritis (RA) (2.5%), primary Sjögren's syndrome (pSS) (1.7%), ankylosing spondylitis (AS) (1.5%), etc. Of females, SLE also showed the highest prevalence (6%), while of males, AS showed the highest prevalence (1.9%). The prevalence of most SARDs was closely associated with age, except mixed connective tissue disease (MCTD), and the variation characteristics among different age groups were different among various SARDs. The prevalence of ANA was significantly increased in most SARD patients [especially in SLE, systemic sclerosis (SSc) and MCTD]. For anti‐ENA antibodies, in contrast to some autoantibodies associated with multiple SARDs (e.g. anti‐SSA, SSB, nRNP), others were relatively specific for certain diseases, such as anti‐dsDNA, Sm, histone, nucleosome and Rib‐P for SLE, anti‐SCL‐70 for SSc and anti‐Jo‐1 for polymyositis/dermatomyositis (PM/DM). Of note, ANA profile appeared to be of little significance for AS, ANCA‐associated vasculitis (AAV), polymyalgia rheumatic (PMR), adult‐onset Still's disease (ASD) and Behcet's disease (BD). The younger were more likely to have the presence of anti‐dsDNA, Sm, histone or Rib‐P for SLE, and anti‐SSA for RA or MCTD. No significant differences for frequencies of ANA and anti‐ENA autoantibodies were found between sexes in most SARDs, with the exception of RA and AS. The present study suggests that, of patients with SARDs‐like clinical manifestations, the proportion of those with true SARDS is small, for most of whom tests for autoantibodies are necessary and useful to help make a prompt and precise diagnosis.     

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.     

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。     

Prevalence of viral hepatitis B and C in riverside communities of the Tucuruí Dam,Pará, Brazil

Epidemiologically, the relevance of infection caused by hepatitis viruses is related mainly to their wide geographic distribution and the large number of infected individuals in all parts of the world. In this study, 668 residents from the islands around the Tucuruí Dam were selected. Blood samples were collected for investigation of serological markers (HBsAg, total anti‐HBc, anti‐HBS, and anti‐HCV) by enzyme immunoassays. HCV‐positive subjects were tested using RT‐PCR and RFLP for the identification of viral genotypes. Among the 668 subjects studied, 1.9% were HBsAg positive, 28% were total anti‐HBc positive, and 41.9% were anti‐HBs positive. The anti‐HBs marker alone (vaccine response) was detected in 25.7% of the volunteers. Anti‐HCV antibody was detected in 2.2% of the subjects and genotype 1 was the predominant genotype (70%). The results indicate an intermediate level of HBV and HCV endemicity in the region studied, as well as low HBV vaccination coverage. J. Med. Virol. 84:1907–1912, 2012. © 2012 Wiley Periodicals, Inc.     

Anti-C1q antibodies in hepatitis C virus infection

Autoantibodies against C1q have been described in many immune-complex diseases including hypocomplementaemic urticarial vasculitis and systemic lupus erythematosus (SLE). No study has focused on the role of anti-C1q antibodies in hepatitis C virus (HCV) infection. The aim of this study was (i) to evaluate the prevalence of anti-C1q antibodies in HCV infection; and (ii) to analyse the association of anti-C1q antibodies with clinical and biological features of HCV-mixed cryoglobulinaemia (MC) vasculitis. We searched for anti-C1q antibodies using an enzyme-linked immunosorbent assay (ELISA) test in 111 HCV patients (75 had cryoglobulin and 23 systemic vasculitis), 60 SLE patients and 109 blood donors. Anti-C1q antibodies were detected in 26% of HCV patients compared to 10% of healthy donors (P < 0.01), and 38% in patients with SLE. Although there was a higher prevalence of anti-C1q antibodies among HCV patients with type III cryoglobulin (50%, P < 0.01), the overall prevalence of anti-C1q antibodies was similar in HCV patients being cryoglobulin-positive or cryoglobulin-negative (26%versus 25%, P = 0.98). A significant association was found between anti-C1q antibodies and low C4 fraction of complement (P < 0.05). No association was found between anti-C1q antibodies and HCV genotype, severity of liver disease or with specific clinical signs of HCV-MC vasculitis. This study shows an increased prevalence of anti-C1q antibodies in HCV-infected patients. Anti-C1q antibodies were associated with low C4 levels. No association was found between anti-C1q antibodies and HCV-MC vasculitis, nor between anti-C1q antibodies and cryoglobulinaemia.     

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.     

Autoantibodies associated with primary biliary cholangitis are common among patients with systemic lupus erythematosus even in the absence of elevated liver enzymes

Knowledge of concomitant autoimmune liver diseases (AILD) is more detailed in primary Sjögren’s syndrome (pSS) compared to systemic lupus erythematosus (SLE). Herein, the prevalence of autoantibodies associated with autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC) was investigated in stored sera from patients with SLE (n = 280) and pSS (n = 114). Antibodies against mitochondria (AMA), liver–kidney microsomal (LKM) antigen, smooth muscle (SMA) and anti‐nuclear antibodies (ANA) were analysed with immunofluorescence microscopy. In addition, AILD‐associated autoantibodies were tested with immunoblot. Prior to sampling, eight SLE (2·9%) and three pSS (2·6%) cases were diagnosed with AILD. Among SLE‐cases without known AILD (n = 272), 26 (9·6%) had PBC‐associated autoantibodies, 15 (5·5%) AIH‐associated autoantibodies (excluding ANA) and one serological overlap. Most subjects with PBC‐associated autoantibodies had liver enzymes within reference limits (22 of 27, 81%) or mild laboratory cholestasis (two of 27, 7·4%), while one fulfilled the diagnostic PBC‐criteria. AMA‐M2 detected by immunoblot was the most common PBC‐associated autoantibody in SLE (20 of 272, 7·4%). The prevalence of SMA (4·4%) was comparable with a healthy reference population, but associated with elevated liver enzymes in four of 12 (25%), none meeting AIH‐criteria. The patient with combined AIH/PBC‐serology had liver enzymes within reference limits. Among pSS cases without known AILD (n = 111), nine (8·1%) had PBC‐associated, 12 (10·8%) AIH‐associated autoantibodies and two overlapped. PBC‐associated autoantibodies were found as frequently in SLE as in pSS but were, with few exceptions, not associated with laboratory signs of liver disease. Overall, AILD‐associated autoantibodies were predominantly detected by immunoblot and no significant difference in liver enzymes was found between AILD autoantibody‐negative and ‐positive patients.     

Valuable antibody detection method for classifying hepatitis E virus genotypes

Nucleotide‐based methods are conventionally used to classify the hepatitis E virus (HEV) genotypes. A serological enzyme immunoassay (EIA) using open reading frame 3 (ORF3) C‐terminal peptides was developed to conveniently and accurately classify and evaluate the genotypes of HEV. The sera of mice immunized with HEV genotype 1, 3, and 4 reacted highly specifically to the peptides of the corresponding genotypes. Most (84.2%) clinical sera infected with HEV genotype 4 were positive for anti‐HEV antibodies when tested with the ORF3 peptides of genotype 4, but were negative for genotypes 1 and 3. Monkey and clinical serial sera infected with HEV reacted strongly to the homologous genotype ORF3 peptides. The indirect EIAs were more sensitive, with stronger reactivity, than commercial anti‐HEV immunoglobulin G assays when serial sera from monkeys infected with HEV genotype 1 or 4 were tested. All our results indicate that the serological typing EIA assays described in this study are more effective and convenient for the classification of HEV genotypes than molecular approaches, and can be used to screen large numbers of serum samples and differentiate genotypes for the diagnosis of HEV infections.     

Transmission of hepatitis C virus among spouses in Cameroon and the Central African Republic

Heterosexual transmission of hepatitis C virus (HCV) is uncommon, with few studies undertaken in Central Africa. To determine the frequency of inter‐spouse HCV transmission, cross‐sectional studies of elderly individuals in Ebolowa, Cameroon and Nola, Central African Republic, in which, respectively, 24 and 83 long‐term couples had been identified, were examined further. Blood samples were tested for antibody to HCV. Anti‐HCV positive samples were genotyped by phylogenetic analysis of a fragment of the NS5B gene. In Nola, 4 out of 9 (44.4%) wives of anti‐HCV positive husbands and 1 out of 74 (1.4%) wives of anti‐HCV negative husbands were anti‐HCV positive (P < 0.001); in Ebolowa, the corresponding proportions were 10 out of 15 (66.7%) and 3 out of 9 (33.3%) (P = 0.21). After adjustment for age and site‐specific risk factors of HCV infection, HCV seropositivity of the wives remained associated with their husbands' HCV serostatus, significantly so in Nola (P = 0.003) and marginally in Ebolowa (P = 0.06). In 7 out of 14 concordant seropositive couples, the genotype could be determined in both spouses. Four couples were infected with different genotypes, while three were infected with the same genotype. Thus, serological concordance between the spouses was related to a combination of infections acquired independently and inter‐spouse transmission. It could not be determined whether inter‐spouse transmission occurred sexually, through blood–blood contact, or otherwise. Inter‐spouse transmission may have contributed to the high prevalence among elderly populations of Central Africa since some patients infected during healthcare subsequently transmitted the virus to their spouse. J. Med. Virol. 83:2113–2118, 2011. © 2011 Wiley Periodicals, Inc.     

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.     

Anti-prothrombin antibodies are associated with adverse pregnancy outcome

Citation Marozio L, Curti A, Botta G, Canuto EM, Salton L, Tavella AM, Benedetto C. Anti‐prothrombin antibodies are associated with adverse pregnancy outcome. Am J Reprod Immunol 2011; 66: 404–409 Problem Women with antiphospholipid antibodies (aPL) such as lupus anticoagulant, anticardiolipin antibodies, and anti‐β₂ glycoprotein‐1 antibodies are at high risk of late pregnancy complications, such as severe pre‐eclampsia, placental insufficiency, and fetal loss. It has been observed that aPL consists of a heterogeneous group of antibodies targeting several phospholipid‐binding plasma proteins, including also anti‐prothrombin (anti‐PT), anti‐protein S (anti‐PS), and anti‐protein C (anti‐PC) antibodies. Their potential role in late pregnancy complications is not known. The aim of this work was to investigate the association between those autoantibodies and histories for adverse pregnancy outcome. Method of study Anti‐PT, anti‐PS, and anti‐PC antibodies were evaluated in 163 patients with previous severe pre‐eclampsia, fetal death, and/or placental abruption and in as many women with previous uneventful pregnancies, negative for aPL. Results The prevalence of anti‐PT antibodies was higher in cases than in controls (OR, 95% CI: 10.92, 4.52–26.38). The highest prevalence was observed in subjects with fetal death. Conclusion Anti‐PT antibodies appear to be associated with adverse pregnancy outcome, irrespectively of aPL.