Usefulness of Clinical and Laboratory Criteria for Diagnosing Autoimmune Liver Disease among Patients with Systemic Lupus Erythematosus: An Observational Study

Abnormal liver function tests are frequently observed during follow-up of patients with systemic lupus erythematosus (SLE) but data on co-existence with autoimmune liver diseases (AILD) are scarce. This retrospective study aimed to describe the prevalence of autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC) among well-characterized subjects with SLE. We also evaluated whether the presence of autoantibodies to complement protein 1q (C1q) and/or ribosomal P protein (anti-ribP) are, directly or inversely, associated with AIH, as proposed in some reports. The number of screened patients was 287 (86% females), and all cases were included in a regional Swedish cohort. Each subject of the study population met the 1982 American College of Rheumatology classification criteria and/or the Fries’ diagnostic principle. By applying the simplified diagnostic AIH criteria combined with persistent transaminasemia, 40 (13.9%) cases reached at least “probable AIH”. However, merely 8 of these had been diagnosed with AIH (overall AIH prevalence 2.8%). Neither anti-C1q nor anti-ribP associated significantly with AIH. By applying the recent PBC guidelines, 6 (2.1%) cases were found, but only 3 of them had actually been diagnosed with PBC and one additional subject was not identified by the guidelines (overall PBC prevalence 1.4%). Compared to prevalence data from the general Swedish population, both AIH and PBC were highly overrepresented in our study population. The sensitivity of the diagnostic AIH criteria was impeccable but the specificity was less impressive, mainly due to positive ANA and hypergammaglobulinemia. Based on our findings, among subjects with SLE, the AIH criteria are less useful and liver biopsy combined with detection of other AILD-associated autoantibodies should be performed.

Increased TIM-3+PD-1+ NK cells are associated with the disease activity and severity of systemic lupus erythematosus

It is well established that natural killer (NK) cells are dysregulated in systemic lupus erythematosus (SLE) patients. However, the functions of NK cells and the mechanisms regulated by them in SLE remain incompletely understood. Patients with SLE were recruited from The First Affiliated Hospital of Nanchang University, and their clinical characteristics and treatments were recorded. The expression levels of T cell immunoglobulin mucin-3 (TIM-3) and programmed cell death protein 1 (PD-1) on NK cells were examined using flow cytometry. The correlations between the increase in TIM-3+PD-1+ NK cells in the SLE patients and clinical traits, including inflammatory markers, auto-antibodies, disease activity and severity of SLE, were examined. The TIM-3+NK cells, PD-1+NK cells and TIM-3+PD-1+ NK cells were significantly increased in the SLE patients. The increase in TIM-3+PD-1+ NK cells in the patients with SLE was associated with erythrocyte sedimentation rate, C-reactive protein, anti-double stranded DNA, anti-ribosomal P, SLE disease activity index and clinical features. The frequency of TIM-3+PD-1+NK cells in SLE patients with a cardiovascular disease (CVD) was significantly lower than that in SLE patients without a CVD. Moreover, the increased TIM-3+PD-1+ NK cells were significantly decreased in SLE patients following treatment. The present study suggested that the increased TIM-3+PD-1+ NK cells were associated with the disease activity and severity of SLE and may play a role in SLE pathogenesis.

Immune Response to Enterococcus gallinarum in Lupus Patients Is Associated With a Subset of Lupus-Associated Autoantibodies

Interactions between gut microbes and the immune system influence autoimmune disorders like systemic lupus erythematosus (SLE). Recently, Enterococcus gallinarum, a gram-positive commensal gut bacterium, was implicated as a candidate pathobiont in SLE. The present study was undertaken to evaluate the influence of E. gallinarum exposure on clinical parameters of SLE. Since circulating IgG antibodies to whole bacteria have been established as a surrogate marker for bacterial exposure, anti-E. gallinarum IgG antibodies were measured in banked serum samples from SLE patients and healthy controls in the Oklahoma Cohort for Rheumatic Diseases. The associations between anti-E. gallinarum antibody titers and clinical indicators of lupus were studied. Antibodies to human RNA were studied in a subset of patients. Our results show that sera from both patients and healthy controls had IgG and IgA antibodies reactive with E. gallinarum. The antibody titers between the two groups were not different. However, SLE patients with Ribosomal P autoantibodies had higher anti-E. gallinarum IgG titers compared to healthy controls. In addition to anti-Ribosomal P, higher anti-E. gallinarum titers were also significantly associated with the presence of anti-dsDNA and anti-Sm autoantibodies. In the subset of patients with anti-Ribosomal P and anti-dsDNA, the anti-E. gallinarum titers correlated significantly with antibodies to human RNA. Our data show that both healthy individuals and SLE patients were sero-reactive to E. gallinarum. In SLE patients, the immune response to E. gallinarum was associated with antibody response to a specific subset of lupus autoantigens. These findings provide additional evidence that E. gallinarum may be a pathobiont for SLE in susceptible individuals.

AB0449 CLINICAL CHARACTERISTICS AND RISK FACTORS OF SYSTEMIC SCLEROSIS WITH HEMATOLOGIC SYSTEM DAMAGES

Background:SSc characterized by varying degrees of fibrosis of the skin and internal organs, clinicians pay more attention to skin and viscera conditions, tend to ignore hematologic system damage. Studies have shown that rheumatic disease such as SLE, RA, pSS often accompanied with hematologic system damages, and hematologic system damages is multiple organ involvement and risk factor of poor prognosis[1-2].Objectives:To investigate the the clinical features, laboratory characteristics and risk factors of Systemic Sclerosis (SSc) patient with hematologic system damages.Methods:The clinical data of 180 patients were collected from January 2010 to April 2020, at the Affiliated Hospital of North Sichuan Medical College. The demographic information, laboratory tests, and clinical symptoms were analyzed retrospectively.Results:Among 180 SSc patients, 70(38.9%) cases were complicated with hematologic system damages. 51(72.9%) cases had anemia, 24 cases (34.3%) had leukopenia, 24 cases (34.3%) had thrombocytopenia, and 22 cases had hematologic system damages associated with more than two cell line involvement. Clinical symptoms: arthritis was significantly higher in the hematologic system damages group than patient without (P<0.05), however, there was no significantly difference in gender, age, disease course, respiratory symptoms, gastrointestinal symptoms, Raynaud’s phenomenon, interstitial lung disease and pulmonary hypertension (all P>0.05). Laboratory tests: ESR and hsCRP were increased in the hematologic system damages group, while the albumin decreased (all P<0.05). The positive rates of resistance to anti-dsDNA antibody and anti-ribosomal P protein antibody was higher in the hematologic system damages group (all P<0.05). Prognosis: During follow-up, leukopenia was more likely to recover, while the thrombocytopenia was more difficult to recover. Logistics regression analysis showed that positive of anti-ribosomal P protein antibody maght be a risk factor for SSc complicated with hematologic system damages [OR = 3.930(P<0.05)] (Table 1).Conclusion:SSc complicated with hematologic system damages is common, and patients with hematologic system damages have more serious clinical symptoms, some of whom have difficulty in recovey. Anti-ribosomal P protein antibody may be a risk factor of SSc hematologic system damages.Table 1.Bivariate logistics regression analysis on risk factors associated with hematologic damages in SSc.FactorBSEWaldOR(95%CI)P valuearthritis0.6540.3473.5431.922(0.973-3.797)0.060ESR-0.0810.4870.0280.922(0.355-2.393)0.868hsCRP-0.0070.4920.0000.993(0.379-2.607)0.989anti-dsDNA0.8680.6731.6642.393(0.637-8.916)0.197anti-Rib-P1.3690.6364.6333.930(1.130-13.666)0.031References:[1]González-Naranjo L A, Betancur O M, Alarcón G S, et al. Features associated with hematologic abnormalities and their impact in patients with systemic lupus erythematosus: Data from a multiethnic Latin American cohort[J]. Seminars in Arthritis and Rheumatism, 2016,45(6):675-683.DOI:10.1016/j.semarthrit.2015.11.003.[2]Skare T, Damin R, Hofius R. Prevalence of the American College of Rheumatology hematological classification criteria and associations with serological and clinical variables in 460 systemic lupus erythematosus patients[J]. Revista Brasileira de Hematologia e Hemoterapia, 2015,37(2):115-119.DOI:10.1016/j.bjhh.2015.01.006Disclosure of Interests:None declared.

Non-ribosomal insights into ribosomal P2 protein in Plasmodium falciparum-infected erythrocytes

The enormous complexity of the eukaryotic ribosome has been a real challenge in unlocking the mechanistic aspects of its amazing molecular function during mRNA translation and many non-canonical activities of ribosomal proteins in eukaryotic cells. While exploring the uncanny nature of ribosomal P proteins in malaria parasites Plasmodium falciparum, the 60S stalk ribosomal P2 protein has been shown to get exported to the infected erythrocyte (IE) surface as an SDS resistant oligomer during the early to mid trophozoite stage. Inhibiting IE surface P2 either by monoclonal antibody or through genetic knockdown resulted in nuclear division arrest of the parasite. This very strange and serendipitous finding has led us to explore more about un-canonical cell biology and structural involvement of P2 protein in Plasmodium in the search for a novel biochemical role during parasite propagation in the human host.

A young lady with ANA negative SLE and Secondary Antip Phospholipid Syndrome

A B S T R A C TSystemic lupus erythematosus (SLE) is a chronic, inflammatory,autoimmune, multisystem connective multi system connective tissuedisease characterized by various autoantibodies to nuclear and cytoplasmicantigens and commonly affects the joints and a variety of organs due to anover activation of the body's immune system. There is wide heterogeneity inpresentation of SLE patients, including lung, central nervous system, skin,kidney, and hematologic manifestations. The presence of antinuclearantibodies (ANA) in serum is generally considered a decisive diagnostic signof SLE. However, a small subset of SLE patients who had the typical clinicalfeatures of SLE was reported to show persistently negative ANA tests. Ourreport describes a 24-yr-old female who presented with the clinicalmanifestations of SLE such as malar rash, photosensitivity, arthritis, oralulcer, and proteinuria. The serum autoantibodies were all negative exceptanti ribosomal P. She was also positive for lupus anticoagulantanti -coagulant. She was treated with oral prednisolone , hydroxychloroquinewith topical tacrolimus, and improved significantly. Three months after,repeat ANA, and anti-ds DNA showed persistent negativity, but lupus anti -coagulant remained positive. This case suggests that ANA may not berequired in the pathogenesis of SLE.