A genome-wide association screen for primary biliary cirrhosis risk alleles was performed in an Italian cohort. The results from the Italian cohort replicated IL12A and IL12RB associations, and a combined meta-analysis using a Canadian dataset identified newly associated loci at SPIB (P = 7.9 × 10–11, odds ratio (OR) = 1.46), IRF5-TNPO3 (P = 2.8 × 10–10, OR = 1.63) and 17q12-21 (P = 1.7 × 10–10, OR = 1.38).

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery datasets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5×10−8) and used pathway analysis to identify JAK-STAT/IL12/IL27 signaling and cytokine-cytokine pathways, for which relevant therapies exist.

Coronavirus disease 2019 (COVID-19) is often associated with interstitial pneumonia. However, there is insufficient knowledge on the presence of autoimmune serological markers in patients with COVID-19. We analyzed the presence and role of autoantibodies in patients with COVID-19-associated pneumonia. We prospectively studied 33 consecutive patients with COVID-19, 31 (94%) of whom had interstitial pneumonia, and 25 age-and sex-matched patients with fever and/or pneumonia with etiologies other than COVID-19 as the pathological control group. All patients were tested for the presence of antinuclear antibodies (ANAs), antiantiphospholipid antibodies (APLs), and anti-cytoplasmic neutrophil antibodies (ANCAs). Clinical, biochemical, and radiological parameters were also collected. Fifteen of 33 (45%) patients tested positive for at least one autoantibody, including 11 who tested positive for ANAs (33%), 8 who tested positive for anti-cardiolipin antibodies (IgG and/or IgM) (24%), and 3 who tested positive for anti-β2-glycoprotein antibodies (IgG and/or IgM) (9%). ANCA reactivity was not detected in any patient. Patients that tested positive for autoantibodies had a significantly more severe prognosis than other patients did: 6 of 15 (40%) patients with autoantibodies died due to COVID-19 complications during hospitalization, whereas only 1 of 18 (5.5%) patients who did not have autoantibodies died (p = 0.03). Patients with poor prognosis (death due to COVID-19 complications) had a significantly higher respiratory rate at admission (23 breaths per minute vs. 17 breaths per minute; p = 0.03) and a higher frequency of autoantibodies (86% vs. 27%; p = 0.008). In conclusion, autoantibodies are frequently detected in patients with COVID-19 possibly reflecting a pathogenetic role of immune dysregulation. However, given the small number of patients, the association of autoantibodies with an unfavorable prognosis requires further multicenter studies.

ANA-H and/or SMA-AA does not exclude AIH, the characterAntibodies to nuclei (ANA), smooth muscle (SMA), and ization of ANA and SMA may help to discriminate between liver/kidney microsomes type 1 (anti-LKM1) may occur in the two conditions. As compared with the seronegative counchronic hepatitis C. Distinct subspecificities, including ANA terpart, autoantibody-positive chronic hepatitis C is more with the homogeneous pattern (ANA-H) and SMA with anticommon in females and exhibits a more severe biochemical actin specificity (SMA-AA), are found in autoimmune hepatiand histological activity. The response to IFN therapy, howtis (AIH). This study was performed to characterize the hepaever, is similar. (HEPATOLOGY 1997;26:561-566.) titis C virus (HCV)-associated autoantibodies and to evaluate their influence on the profile of the disease. Two hundred ninety consecutive patients with chronic hepatitis C and 35A variety of immunological abnormalities has been decontrol cases with AIH were screened for autoantibodies by scribed in patients with chronic hepatitis C. In particular, indirect immunofluorescence (IFL) at 1:40 serum dilution. the occurrence of serum non-organ-specific autoantibodies The ANA pattern was defined by IFL on HEp-2 cells and the has been extensively studied: smooth muscle (SMA) and anti-SMA-AA identified by the presence of at least two of the nuclear (ANA) antibodies have been detected in approxifollowing elements: 1) SMA T or SMA G pattern by IFL on mately one third of the cases, 1,2 while antibodies to liver/ kidney sections; 2) XR 1 precipitating system by counterimmu-kidney microsomes type 1 (anti-LKM1) have been found noelectrophoresis; or 3) typical pattern by IFL on liver sec-more rarely (from 0% to 5%). [2][3][4] Variations in the autoantitions from phalloidin-intoxicated rats. ANA, SMA, and anti-body prevalence among the reports so far published 1-7 have LKM1 occurred in 9%, 20%, and 6% of chronic hepatitis C been attributed both to different experimental conditions in cases, respectively. The overall prevalence of autoantibodies the immunofluorescence (IFL) procedure and to ethnical and was 30% (87 of 290). Compared with AIH, HCV-associated geographical differences in the study populations. ANA and SMA exhibited ANA-H and SMA-AA at a lower Most reports agree that the autoantibody positivity does prevalence (38% vs. 71%, P Å .04 and 8% vs. 87%, P õ not influence either the clinical and biochemical profile of .000001, respectively) and had a lower median titer (1:80 vs. chronic hepatitis C or the response to interferon (IFN) alfa. 1:320, P õ .001 and 1:40 vs. 1:320, P õ .000001, respec-Some data, however, have been published on the occurrence tively). The concomitant positivity for ANA-H and SMA-AA of disease activity exacerbations in patients with serum autowas detected in none of the HCV cases, but in 46% of AIH antibodies during IFN treatment. 8-10 sera (P õ .000001). Two parameters were independently asThe major impact of the above autoantibodies in the hepasociated with the autoantibodie...