Retrospective review of pediatric and adult autoimmune hepatitis in two quaternary care centres in British Columbia: increased prevalence seen in British Columbia's First Nations community.

BACKGROUND: It has been previously reported that British Columbia's (BC's) First Nations (Aboriginal) community has an increased risk of autoimmune diseases, including rheumatological conditions (rheumatoid arthritis, systemic lupus) and primary biliary cirrhosis. The researchers hypothesized that this community may also be at increased risk for autoimmune hepatitis (AIH). METHODS: Independent, retrospective reviews of the databases of two separate tertiary/quaternary British Columbia university-affiliated health care institutions, the Adult Liver Transplant Program of the BC Transplant Society and the Division of Pediatric Gastroenterology, BC Children's Hospital (Vancouver, BC), were performed. All patients referred with a diagnosis of probable or definite AIH who identified themselves as being of First Nations descent from 1988 to 2004 were reviewed. The liver transplant database records all adult patients in the province referred for transplant assessment. The pediatric database records all children referred to the BC Children's Hospital. RESULTS: A total of 68 adult patients with a definite or probable diagnosis of AIH were referred to the liver transplant program. Twelve patients (17.6%) were Aboriginal, 11 of which were female. Similarly, a total of 30 children with probable or definite AIH were identified from the pediatric database. Six of these cases (20%) were identified in Aboriginal children. CONCLUSIONS: The findings suggest an increased prevalence of AIH among BC's First Nations community. A disproportionate First Nations representation was found on independent review of two databases. Future studies are needed to determine the true prevalence of AIH in this community, and to uncover the genetic predisposition and the environmental triggers explaining this phenomenon.     

Autoimmune liver disease Aboriginal Communities Northwest and the Canadian First Nations of British Columbia＇s Pacific

Primary biliary cirrhosis (PBC) is a well-known but uncommon chronic liver disease that is presumed to be of autoimmune etiology. Recently, investigations in British Columbia (BC), a province of Canada situated along the Pacific North-West of North America, have suggested that PBC is not a rare disease amongst BC's Aboriginal (i.e. First Nations) communities. Geographically, BC is adjacent to South East Alaska, an American state that has also reported an increased prevalence of PBC amongst its Aboriginal communities. In this article, the medical evidence supporting a hypothesis of increased risk of PBC amongst BC's First Nations communities is reviewed. Evidence suggesting that autoimmune hepatitis is also more likely amongst BC's First Nations communities is also presented.     

Indications for liver transplantation in British Columbia's Aboriginal population: a 10-year retrospective analysis.

OBJECTIVES: To study the indications for liver transplantation among British Columbia's First Nation population. MATERIALS AND METHODS: A retrospective analysis of the British Columbia Transplant Society's database of Aboriginal and non-Aboriginal liver transplant recipients from 1989 to 1998 was undertaken. For primary biliary cirrhosis (PBC), the transplant assessment database (patients with and without transplants) was analyzed using a binomial distribution and compared with published census data regarding British Columbia's proportion of Aboriginal people. RESULTS: Between 1989 and 1998, 203 transplantations were performed in 189 recipients. Fifteen recipients were Aboriginal (n=15; 7.9%). Among all recipients, the four most frequent indications for liver transplantation were hepatitis C virus (HCV) infection (n=57; 30.2%), PBC (n=34; 18.0%), alcohol (n=22; 11.6%) and autoimmune hepatitis (n=14; 7.4%). Indications for liver transplantation among Aboriginal people were PBC (n=8; 53.3%; P<0.001 compared with non-Aboriginal people), autoimmune hepatitis (n=4; 26.67%; P=0.017), acute failure (n=2; 13.3%) and HCV (n=1). Among all patients referred for liver transplantation with PBC (n=43), 29 (67.44%) were white and 11 (25.6%) were Aboriginal. A significant difference was found between the proportion of Aboriginal people referred for liver transplantation and the proportion of Aboriginal people in British Columbia (139,655 of 3,698,755 [3.8%]; 1996 Census, Statistics Canada) (P<0.001). CONCLUSIONS: Aboriginal people in British Columbia are more likely to be referred for liver transplantation with a diagnosis of PBC but are less likely to receive a liver transplant because of HCV or alcohol than are non-Aboriginal people.     

Increased prevalence of primary sclerosing cholangitis among first-degree relatives

BACKGROUND/AIMS: The aim of the present study was to investigate the familial occurrence of autoimmune diseases in a large group of patients with primary sclerosing cholangitis (PSC). METHODS: All patients with PSC treated at Huddinge University Hospital between 1984 and 1999 were included (n=145). For every patient with PSC and inflammatory bowel disease (IBD) (n=126) we randomly selected a control patient with IBD (n=126), matched for age, sex and type of IBD. A questionnaire comprising information about autoimmune diseases among first-degree relatives was answered by all patients and controls. RESULTS: We identified 22 index cases with PSC from 21 families with a first-degree relative with either chronic liver disease and/or IBD. Five patients with PSC had a first-degree relative with PSC (3.4%). The prevalence of PSC among first-degree relatives was 0.7% (5/717). In siblings the prevalence was 1.5% (4/269). The prevalence of first-degree relatives with autoimmune diseases outside the liver was similar in PSC patients and controls. CONCLUSIONS: First-degree relatives of patients with PSC have a PSC prevalence of 0.7%. This represents a nearly 100-fold increased risk of developing PSC compared with the general population, supporting the hypothesis that genetic factors are of importance for development of PSC.     

Quality of life and everyday activities in patients with primary biliary cirrhosis

Primary biliary cirrhosis (PBC) is generally a slowly progressive disease that may lead to cirrhosis and liver failure. However, patients with PBC often suffer from a variety of symptoms long before the development of cirrhosis that include issues of daily living that have an impact on their work environment and their individual quality of life. We therefore examined multiple parameters by taking advantage of the database of our cohort of 1032 patients with PBC and 1041 matched controls. The data were obtained from patients from 23 tertiary referral centers throughout the United States and from rigorously matched controls by age, sex, ethnicity, and random-digit dialing. The data showed that patients with PBC were more likely than controls to have significant articular symptoms, a reduced ability to perform household chores, and the need for help with routine activities. Patients with PBC rated their overall activity similar or superior to that of controls; however, more of them reported limitations in their ability to carry out activities at work or at home and difficulties in everyday activities. PBC cases also more frequently reported limitations in participating in certain sports or exercises and pursuing various hobbies; however, they did not report significant limitations in social activities. In a multivariable analysis, household income, a diagnosis of systemic lupus erythematosus, limitations in work activities, a reduction in work secondary to disability, and church attendance were independently increased in PBC cases with respect to controls. CONCLUSION: Our data indicate that the quality of life of patients with PBC in the United States is generally well preserved. Nevertheless, patients with PBC suffer significantly more than controls from a variety of symptoms that are beyond the immediate impact of liver failure and affect their lifestyle, personal relationships, and work activities.     

Further evidence for a strong genetic influence on the development of autoimmune thyroid disease: the California twin study.

To determine the heritable component of Graves' disease (GD) more precisely, a disease survey questionnaire completed by 13,726 California-born twin pairs over the age of 37 years was used as the foundation of this study. On the basis of this survey, each member of pairs reporting a past diagnosis of GD was then sought for an extensive telephone interview to seek diagnostic confirmation. Successful diagnostic evaluation occurred in 108 cases, of which 99 affected twin pairs form the basis of this report. The results indicate that the estimated pairwise concordance for is 17% in monozygotic (MZ) twins, and 1.9% in dizygotic (DZ) twins, which are in close agreement with a recent report from a Danish twin population. Moreover, the reported 3.9% occurrence of GD found in the first-degree relatives of affected twin pairs supports these findings. In contrast, only 0.45% of all twins, 0.27% of the spouses of twins, and approximately 0.16% of the first-degree relatives of unaffected twins were reported to have GD. Additionally, among the unaffected MZ twins of patients with GD, 17% reported having chronic thyroiditis and 10% other nonthyroid autoimmune conditions such as lupus erythematosus, pernicious anemia, or idiopathic thrombocytopenic purpura. Thus, a genetic predisposition appears to be shared for both thyroid and some nonthyroid autoimmune diseases. While it seems that GD is a strongly and nonspecifically heritable condition, the relatively low level of twin concordance indicates that this disease likely requires a nonheritable etiologic determinant(s) as well.     

Prevalence of systemic lupus erythematosus and systemic sclerosis in the First Nations population of Alberta, Canada

Objective

To estimate the population‐based prevalence of systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) in Alberta, Canada, stratified by First Nations status.

Methods

Physician billing claims and hospitalization data for the province of Alberta (1994–2007) were used to ascertain cases of SLE and SSc using 3 case definitions. A latent class Bayesian hierarchical regression model was employed to account for the imperfect sensitivity and specificity of billing and hospitalization data in case ascertainment. We accounted for demographic factors, estimating prevalence rates for the First Nations and non–First Nations populations by sex, age group, and location of residence (urban/rural).

Results

Our model estimated the prevalence of SLE in Alberta to be 27.3 cases per 10,000 females (95% credible interval [95% CrI] 25.9–28.8) and 3.2 cases per 10,000 males (95% CrI 2.6–3.8). The overall prevalence of SSc in Alberta was 5.8 cases per 10,000 females (95% CrI 5.1–6.5) and 1.0 case per 10,000 males (95% CrI 0.7–1.4). First Nations females over 45 years of age had twice the prevalence of either SLE or SSc relative to non–First Nations females. There was also a trend toward higher overall SLE prevalence in urban dwellers, and higher overall SSc prevalence in rural residents.

Conclusion

First Nations females older than 45 years of age have an increased prevalence of either SLE or SSc. This may reflect a true predominance of autoimmune rheumatic diseases in this demographic, or may indicate systematic differences in health care delivery.     

Antimitochondrial antibodies and reactivity to N. aromaticivorans proteins in Icelandic patients with primary biliary cirrhosis and their relatives

OBJECTIVES: Primary biliary cirrhosis (PBC) is a chronic, progressive cholestatic disease of unknown etiology characterized by serum antimitochondrial antibodies (AMA) directed against a functionally related family of mitochondrial enzymes. We recently suggested that N. aromaticivorans might be the trigger of autoimmunity in PBC. No data are available on the specificity and crossreactivity of AMA in a genetically homogenous group of patients, such as the Icelandic population. METHODS: To address these issues and to confirm previous findings in a unique population, we obtained sera from 14 PBC patients and 85 first-degree relatives, all of Icelandic descent. We analyzed such sera for AMA specificity using recombinant mitochondrial antigens and for reactivity against N. aromaticivorans proteins. RESULTS: Thirteen of the 14 Icelandic patients with PBC (93%) were found AMA positive. We found that 5/13 AMA positive sera (38%) reacted against PDC-E2 only; 5/13 (or 38%) reacted against BCOADC-E2; and 2/13 (15%) reacted against all three antigens. There was no reactivity against OGDC-E2. Reactivities of patients' sera against N. aromaticivorans were consistent with the AMA status. One serum among the 85 first-degree relatives (1.2%) was found to be AMA-positive, as well as reactive against N. aromaticivorans. CONCLUSIONS: Interestingly, despite the homogenous genetic background, the group of Icelandic patients with PBC was heterogeneous in their AMA reactive patterns and also reacted with N. aromaticivorans proteins.     

Involvement of the liver in rheumatic diseases

Liver dysfunction is often observed in patients with rheumatic diseases. Underlying disease is the major cause of liver dysfunction associated with adult-onset Still’s disease, polymyositis/dermatomyositis, and vasculitis syndrome, whereas drug-induced liver injury is common in rheumatoid arthritis and systemic lupus erythematosus. These diseases may be accompanied by autoimmune hepatitis and primary biliary cirrhosis (PBC). PBC is particularly common in CREST (calcinosis, Raynaud’s phenomenon, esophageal dysmotility, sclerodactylia, and telangiectasia) syndrome and Sj?gren’s syndrome. The recent widespread use of biological drugs such as tumor necrosis factor inhibitors has raised concerns about reactivation of hepatitis B. Given the varying causes and degrees of liver dysfunction associated with rheumatic diseases, medical intervention should be undertaken with adequate understanding of the characteristics of each type of liver disease.     

High levels of a common anti-DNA idiotype (16/6), a genetic marker for SLE

Six out of 8 healthy first-degree relatives of a patient with systemic lupus erythematosus (SLE) had very high serum levels of a common anti-DNA idiotype (16/6). In this family an additional sister developed SLE, and all members were heterozygous for C4 deficiency. Measurements of common autoantibody idiotypes may contribute to the understanding of the genetics of autoimmune diseases. They might be found useful in detecting healthy subjects prone to the development of an overt clinical state.     

Risk factors and comorbidities in primary biliary cirrhosis: a controlled interview-based study of 1032 patients

Primary biliary cirrhosis (PBC) is an autoimmune disease of unknown etiology, often associated with other autoimmune conditions. Controlled studies have so far provided conflicting data on risk factors and comorbidity rates in PBC. We enrolled patients with PBC (n = 1032) from 23 tertiary referral centers for liver diseases in the United States and random-digit-dialed controls (n = 1041) matched for sex, age, race, and geographical location. Patients and controls were administered a modified version of the US National Health and Nutrition Examination Study (NHANES III) questionnaire by trained personnel to evaluate associations between PBC and social, demographic, personal and family medical histories, lifestyle, and reproductive factors and the rates of comorbidity in affected individuals. Data indicate that having a first-degree relative with PBC (adjusted odds ratio [AOR] 10.736; 95% confidence interval 4.227-27.268), history of urinary tract infections (AOR 1.511, 95% CI 1.192-1.915), past smoking (AOR 1.569, 95% CI 1.292-1.905), or use of hormone replacement therapies (AOR 1.548, 95% CI 1.273-1.882) were significantly associated with increased risk of PBC. The frequent use of nail polish slightly increased the risk of having PBC. Other autoimmune diseases were found in 32% of cases and 13% of controls (P<0.0001). In conclusion, environmental factors, possibly including infectious agents through urinary tract infections or chemicals contained in cigarette smoke, may induce PBC in genetically susceptible individuals. Exogenous estrogens may also contribute to explain the female predominance of the disease.     

Diagnosing clinical subsets of autoimmune liver diseases based on a multivariable model

Background Diagnosing autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), primary sclerosing cholangitis, and other autoimmune liver diseases remains an imperfect process. We need a more accurate, evidence-based diagnostic system. Methods We conducted a national survey and identified 988 cases of liver disease which did not satisfy the inclusion criteria for any liver disease of known etiology. We expected these cases to include autoimmune liver disease (AILD) and its variant forms. We selected 269 prototype cases for which histological re-evaluation of liver biopsy by independent expert hepatopathologists and the original diagnosis coincided. We did a multiple logistic regression analysis to determine explanatory variables that would distinguish cases of AIH and PBC from those of non-AIH and non-PBC, respectively. We constructed a multivariable diagnostic formula that gave AIH and PBC disease probabilities and validated it in a study of an additional 371 cases (validation group). Results Based on the results of the statistical analysis, we selected three laboratory tests and four histological features as independent variables correlated to the diagnosis of both AIH and PBC. For the validation group, assuming that the original diagnosis was correct, the sensitivity and specificity for AIH were 86.3% and 92.4%, respectively. For PBC the sensitivity and specificity were 82.5% and 63.7%, respectively. A detailed analysis of inconsistent cases showed that the diagnosis based on the formula had given the correct diagnosis, for either AIH or PBC, except for 5 cases (1.3%) in which disease probability was low for both. Conclusions A seven-variable formula based on three laboratory tests and four histological features gives significant information for the diagnosis of AILD.     

Detection of anti-double and anti-single stranded DNA antibodies in chronic liver disease: Significance of anti-double stranded DNA antibody in autoimmune hepatitis

Anti-DNA antibodies were determined by an enzyme-linked immunosorbent assay in 116 patients with chronic liver disease consisting of 21 cases of autoimmune hepatitis (AIH), 17 of primary biliary cirrhosis (PBC), and 78 of non-autoimmune-type of chronic liver disease. The assay was also performed on 83 patients with collagen disease, as a control group. Anti-double stranded DNA antibody (anti-dsDNA) was detected in 10/21 (48%) of the AIH patients and in 3/17 (17%) of the PBC patients, but not in those with other liver diseases. In contrast, anti-single stranded DNA antibody (anti-ssDNA) was positive not only in AIH and PBC, but also in those with non-autoimmune-types of chronic liver disease. Follow-up liver histology disclosed that the 2 patients with AIH who were positive for anti-dsDNA developed liver cirrhosis, whereas the 4 patients who were negative for anti-dsDNA, and those who showed a disappearance of anti-dsDNA following corticosteroid therapy, improved from chronic active to chronic persistent hepatitis.     

Genetic studies of Ro (SS-A) and La (SS-B) autoantibodies in families with systemic lupus erythematosus and primary Sj?gren's syndrome

Using enzyme-linked immunosorbent assays, autoantibodies to Ro (SS-A) were detected in the sera of 21% of the first-degree relatives and 11% of the second-degree relatives of anti-Ro-positive probands with systemic lupus erythematosus (SLE) or primary Sj?gren's syndrome, as compared with 3% of normal control subjects (P = 0.003 and P = 0.09, respectively). In a parallel study, anti-Ro occurred in 28% of the first-degree relatives of unselected members of families of SLE patients, regardless of the proband's serologic status, compared with 6% of the relatives from normal healthy families. Antibodies to La and to Sm/nuclear RNP were infrequent. Anti-Ro occurred in 41% of the relatives considered to have a dominant, non-HLA-linked "autoimmune trait" by virtue of having any autoimmune disorder and/or serologic abnormality (antinuclear antibodies, anti-single-stranded DNA, or biologic false-positive VDRL test result), as compared with only 2% of the healthy, seronegative relatives without the trait (P = 0.009). Moreover, HLA-DR2 and/or DR3 occurred in 90% of anti-Ro-positive subjects, regardless of their clinical status. These results demonstrate that the Ro autoantibody response occurs frequently in relatives of patients with SLE and is genetically mediated by both major histocompatibility complex and non-major histocompatibility complex effects.     

原发性胆汁性胆管炎患者血清自身抗体和临床特征分析*

目的 原发性胆汁性胆管炎(PBC)是我国常见的一种自身免疫性肝病,本研究对PBC患者血清自身抗体阳性情况和临床特征进行了分析,以期为其临床诊治提供参考。方法 回顾性分析我院住院诊治的230例PBC患者的临床资料,采用欧盟试剂检测血清抗线粒体抗体(AMA和AMA-M2)、抗核糖核蛋白(RNP)抗体、抗SSA60、抗SSA52、抗SSB、抗着丝点蛋白B(CENP-B)、抗双链DNA(dsDNA)、抗组蛋白、抗Sp100、抗gp210和抗核小体抗体(ANua)等。分析合并其他自身免疫性疾病,包括干燥综合征(SS)和系统性红斑狼疮(SLE)等。结果 在230例PBC患者中,AMA-M2阳性167例(72.6%),抗gp210阳性101例(43.9%),抗Sp100阳性39例(17.0%);在所有PBC患者中,有178例(77.4%)ANA阳性;血清抗SSA52和抗CENP-B阳性率分别为37.4%和20.0%;在所有PBC患者中,合并SS者54例(23.5%),合并SLE者 21例(9.1%);与156例代偿期肝硬化比,74例失代偿期患者血清抗gp210和抗SSA52阳性率显著升高,分别为63.5%对34.6%(P<0.05)和(44.6%对29.5%,P<0.05),差异有统计学意义。结论 本研究发现血清AMA-M2、抗gp210和抗Sp100等仍然是诊断PBC的特征性指标。PBC患者血清抗SSA52和抗CENP-B阳性率也较高,可以作为补充诊断的潜在指标。本研究还发现血清抗gp210和抗SSA52阳性可能提示PBC病情较严重。SS和SLE作为PBC患者的常见合并症,其具体的发病机制和与疾病进程的关系,仍值得我们进一步的深入研究。     

Autoimmune disease aggregation in families with primary Sjögren's syndrome

OBJECTIVE: Diverse autoimmune diseases may coexist in the same individual and in families, implying a common etiology. We examined the aggregation of autoimmune diseases among first-degree relatives (FDR) of patients with primary Sj?gren's syndrome (pSS). METHODS: This was a population-based case-control family study in which 101 families of women classified as having pSS according to the revised American-European criteria and 124 families of matched controls without autoimmune disease were enrolled to investigate the presence of autoimmune diseases. We performed a genetic analysis that included familial correlation and recurrent risk ratios. RESULTS: In family cases, 38% had at least one FDR with an autoimmune disease, versus 22% in control families [odds ratio (OR) 2.2, 95% confidence interval (CI) 1.2-3.9, p = 0.01]. An autoimmune disease was registered for 7.3% of 876 patients' FDR as compared with 3.85% of 857 controls' FDR (OR 1.97, 95% CI 1.28-3.03, p = 0.002). The most frequent autoimmune diseases registered among the pSS patients' FDR were autoimmune thyroid disease (AITD), systemic lupus erythematosus, and rheumatoid arthritis, which disclosed aggregation. The proband phenotype (i.e., pSS) was correlated with AITD, systemic sclerosis, and all autoimmune diseases when considered together as a trait. Maternal transmission of the autoimmunity trait was observed in cases but not in controls. CONCLUSION: Our results indicate that autoimmune diseases cluster within families of patients with pSS. This familial aggregation of autoimmune diseases adds further evidence that clinically different autoimmune phenotypes might share common susceptibility gene variants, which acting in epistatic pleitropy may represent risk factors for autoimmunity.     

Clinical and laboratory characteristics of Finnish lupus erythematosus patients with cutaneous manifestations

Our objective was to characterize clinical features, laboratory findings, concomitant autoimmune diseases, and smoking habits of lupus erythematosus subgroups in genetically homogeneous patients from two Dermatology Departments of Finnish University hospitals. One hundred and seventy eight discoid lupus erythematosus, 55 subacute cutaneous lupus erythematosus, and 77 systemic lupus erythematosus patients were enrolled using patients' charts from institutional database (1995-2006) and during routine control visits. Clustering analysis was performed to reveal natural groupings. Smoking at the onset of disease was significantly more common in all subgroups (57% for discoid lupus erythematosus, 35% for subacute cutaneous lupus erythematosus, and 34% for systemic lupus erythematosus) compared with the age/gender-matched prevalence in the Finnish population, suggesting smoking to be a trigger factor for cutaneous lupus. Leukopenia (38%) and lymphopenia (52%) were observed more often in patients with systemic lupus erythematosus than reported previously. Photosensitivity characterized all groups, especially patients with subacute cutaneous lupus erythematosus (87%). Of the autoimmune diseases, Sj?gren's syndrome was the most common (22% of patients with systemic lupus erythematosus), followed by autoimmune thyroid disease (13% of patients with subacute cutaneous lupus erythematosus). The clustering analysis showed environmental factors (smoking) to be more involved in disease development in discoid lupus erythematosus, whereas immunological factors were more significant in initiating systemic lupus erythematosus. The high prevalence of autoimmune thyroid disease, together with photosensitivity, and the clustering profiles suggest that lupus erythematosus subtypes, especially discoid lupus erythematosus, are heterogeneic in their pathomechanisms.     

Prevalence of autoimmune inflammatory myopathy in the first nations population of Alberta,Canada

Objective

To estimate the population‐based prevalence of autoimmune inflammatory myopathy (AIM) in Alberta, Canada, with a specific focus on rates in the First Nations population.

Methods

Physician billing claims and hospitalization data for the province of Alberta (1994–2007) were used to estimate the probability of having AIM (i.e., polymyositis or dermatomyositis) based on 3 case definitions. A latent class Bayesian hierarchical regression model was employed to account for the imperfect sensitivity and specificity of billing and hospitalization data in case ascertainment. We accounted for demographic factors of sex, age group, and location of residence (urban or rural) in estimating the prevalence rates within the First Nations and non–First Nations populations.

Results

The overall prevalence of AIM was 25.0 per 100,000 persons (95% credible interval [95% CrI] 13.4–49.0) in the First Nations population and 33.8 (95% CrI 28.9–39.6) in the non–First Nations population. For both groups, prevalence was increased in women relative to men, rural women relative to urban women, and in those age >45 years.

Conclusion

Unlike other rheumatic diseases such as rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis, we did not detect an increased prevalence of AIM in Alberta's First Nations population relative to the non–First Nations population. Potential limitations include coding errors, underidentification of First Nations members, and recognized differences in access to care for the First Nations population.     

Primary biliary cirrhosis-specific autoantibodies in first degree relatives of Greek primary biliary cirrhosis patients

AIM: To determine the prevalence and significance of primary biliary cirrhosis (PBC)-specific autoantibodies in first-degree relatives (FDRs) of Greek PBC patients.METHODS: The presence of antimitochondrial antibodies (AMA) and PBC-specific antinuclear antibodies (ANA) were determined using indirect immunofluorescence assays, dot-blot assays, and molecularly based enzyme-linked immunosorbent assays in 101 asymptomatic for liver-related symptoms FDRs of 44 PBC patients. In order to specify our results, the same investigation was performed in 40 healthy controls and in a disease control group consisting of 40 asymptomatic for liver-related symptoms FDRs of patients with other autoimmune liver diseases namely, autoimmune hepatitis-1 or primary sclerosing cholangitis (AIH-1/PSC).RESULTS: AMA positivity was observed in 19 (only 4 with abnormal liver function tests) FDRs of PBC patients and none of the healthy controls. The prevalence of AMA was significantly higher in FDRs of PBC patients than in AIH-1/PSC FDRs and healthy controls [18.8%, 95% confidence interval (CI): 12%-28.1% vs 2.5%, 95% CI: 0.1%-14.7%, P = 0.01; 18.8%, 95% CI: 12%-28.1% vs 0%, 95% CI: 0%-10.9%, P = 0.003, respectively]. PBC-specific ANA positivity was observed in only one FDR from a PSC patient. Multivariate analysis showed that having a proband with PBC independently associated with AMA positivity (odds ratio: 11.24, 95% CI: 1.27-25.34, P = 0.03) whereas among the investigated comorbidities and risk factors, a positive past history for urinary tract infections (UTI) was also independently associated with AMA detection in FDRs of PBC patients (odds ratio: 3.92, 95% CI: 1.25-12.35, P = 0.02).CONCLUSION: In FDRs of Greek PBC patients, AMA prevalence is significantly increased and independently associated with past UTI. PBC-specific ANA were not detected in anyone of PBC FDRs.     

Anti-NMDA receptor autoantibodies in patients with systemic lupus erythematosus and their first-degree relatives

The objective of this study is to investigate the presence of autoantibodies cross-reacting with the NR2 subunit of the N-methyl-d-aspartate (NMDA) glutamate receptor in plasma samples of patients with systemic lupus erythematosus (SLE), in their healthy first-degree relatives and in healthy unrelated individuals and to determine whether these autoantibodies are specific for lupus patients in general or for the subgroup of SLE patients with neuropsychiatric (NP) manifestations. Plasma samples were collected from 51 lupus patients (19 with and 32 without NP manifestations), 161 first-degree relatives and 55 healthy unrelated controls. Antibodies to a linear peptide of the NR2 subunit of the NMDA receptor were determined by enzyme-linked immunosorbent assay. A significant difference in mean antibody reactivity between SLE patients and healthy unrelated controls (P < 0.01) and between firstdegree relatives and healthy unrelated controls (P < 0.001) was found. No difference was found between lupus patients and their first-degree relatives or between lupus patients with and without NP symptoms. In this study, anti-NMDA receptor autoantibodies show more specificity for lupus patients (but not for selected patients with NP symptoms) and their first-degree relatives than for healthy controls, indicating a familial basis to mount an immune response to this peptide.