ACA-positive Patients Research Articles

Stratification according to autoantibody status in systemic sclerosis reveals distinct molecular signatures

ObjectivesSystemic sclerosis (SSc) is a heterogeneous disease, complicating its management. Its complexity and the insufficiency of clinical manifestations alone to delineate homogeneous patient groups further challenge this task. However, autoantibodies...

Cross-sectional study using the University of California, Los Angeles, Scleroderma Clinical Trials Consortium Gastrointestinal Tract Instrument 2.0 (UCLA SCTC GIT 2.0) for gastrointestinal disorders of systemic sclerosis.

This study aimed to identify severe gastrointestinal ailments in patients with systemic sclerosis (SSc), investigate the role of antibodies in gastrointestinal disorders, and explore the relationship between limited cutaneous SSc (lcSSc) and diffuse cutaneous SSc (dcSSc) in terms of gastrointestinal involvement and its association with skin stiffness. We used the University of California, Los Angeles, Scleroderma Clinical Trials Consortium Gastrointestinal Tract Instrument 2.0 (UCLA SCTC GIT 2.0) questionnaire to assess gastrointestinal disturbances in 100 patients with SSc. Gastrointestinal impairment was categorized into three levels: absence of or minor symptoms, moderate symptoms, and severe symptoms, as indicated by the total gastrointestinal tract (GIT) score. Comparing 27 patients with dcSSc and 73 patients with lcSSc, severe gastrointestinal disturbances were found in 7.4% of patients with dcSSc and 4.1% of patients with lcSSc. A total of 18.0% of anticentromere antibody (ACA)-positive patients exhibited moderate to severe symptoms, while 9.1% of antitopoisomerase 1 antibody-positive patients displayed similar symptoms. The average disease duration in patients with severe symptoms was 15.0 years, in those with moderate symptoms was 10.3 years, and in those who were symptom-free or mildly affected was 8.5 years. Among 16 patients with moderate to severe gastrointestinal disorders, a positive correlation was observed between the modified Rodnan skin thickness score (mRSS) and total GIT score. In addition, a positive correlation was identified between fecal incontinence and mRSS, with weaker correlations for reflux and bloating symptoms. Patients with gastrointestinal disorders showed a tendency to worsen over time, particularly in ACA-positive patients with dcSSc. Furthermore, a correlation was observed between mRSS and fecal incontinence, reflux, and abdominal bloating in patients with moderate to severe gastrointestinal disturbances.

P-185 Shortening the time from ovulation trigger to insemination is effective in reducing multiple pronuclei formation in anti-centromere antibody-positive patients

Abstract Study question Does shortening the time from ovulation trigger to insemination reduce multiple pronuclei formation (MPF) and improve the outcome after fertilization? Summary answer Shortening the time from ovulation trigger to insemination increased the normal fertilization rate and increased the number of cycles in which good embryos were obtained. What is known already When anti-centromere antibody (ACA)-positive patients undergo IVF, low oocyte maturation rates and MPF may be observed, which tend to occur when ACA antibody titers are high. In this case, the patient tends to present with poor embryonic development. There is currently no effective treatment for ACA-positive patients. It has been reported that MPF is caused by chromosome dispersion due to significant abnormal spindle deformation. In such cases, it has been reported that the oocyte spindle is often not visualized by polarized light microscopy. The oocyte is affected by ACA during the meiosis, but the mechanism is not well understood. Study design, size, duration A retrospective study was conducted on 764 mature oocytes from 174 cycles in 45 patients who underwent oocyte retrieval and inseminated by intra-cytoplasmic sperm injection (ICSI) with consent from 2009 to 2022. Patients were limited to those who tested positive for ACA by blood antinuclear antibody testing and whose oocytes occurred MPF. Participants/materials, setting, methods Oocyte retrieval was performed 36 hours after ovulation trigger. After ICSI, embryos were cultured until day 3 or blastocyst. The group was divided into two groups: the time reduced from ovulation trigger to ICSI (S group, n = 95) and the normal protocol (N group, n = 79). The normal fertilization rate, MPF rate, the rate of good embryo on day 3, the percentage of IVF cycles with good embryo, and clinical pregnancy rate per transfer were compared. Main results and the role of chance The mean time from maturation trigger to insemination was shorter in the S group than in the N group (38.2h vs. 41.8h, P < 0.01). The normal fertilization rate was significantly increased in the S group compared to the N group (49.9 vs. 40.7, P < 0.01) and the MPF rate was significantly decreased (39.1 vs. 28.3, P < 0.01). The rate of transferable embryo on day 3 tended to increase in the S group compared to the N group (70.6 vs. 61.9, P = 0.09). In addition, the percentage of IVF cycles with good embryo was significantly increased in the S group compared to the N group (57.4 vs. 28.4, P < 0.01). There was no difference in pregnancy rate per embryo transfer. There was no difference in the age of the wife at the time of oocyte retrieval. Limitations, reasons for caution The data were conducted from a single facility. and the limited number of cases, resulting in a small sample size. The process of visualizing the oocyte spindle was not performed in this study because it is time consuming and increases the time from ovulation trigger to insemination. Wider implications of the findings Shortening the time from maturation trigger to insemination was decreased MPF, suggesting that the oocyte spindle is affected by ACA in a time-dependent manner. It is recommended that ICSI be performed as soon as possible after oocyte retrieval. Trial registration number not applicable

Pregnancy outcomes of patients with positive anticentromere antibodies receiving in vitro fertilization-embryo transfer.

To analyze the pregnancy outcomes in patients with positive anti-centromere antibodies (ACA) receiving in vitro fertilization (IVF)-embryo transfer (ET) and natural conception. A case-control study was used to retrospectively analyze the clinical data of 3955 patients who received IVF-ET therapy and had the results of antinuclear antibody (ANA) spectrum at Zhejiang Provincial People's Hospital from June 2016 to June 2023. Patients with positive ACA and negative ACA were matched at a ratio of 1∶3 using propensity score matching. Embryo outcomes of IVF were compared between the two groups, and the impact of different fertilization methods and the use of immunosuppressants on pregnancy outcomes were analyzed using self-matching. The natural conception and disease progress were followed up for ACA-positive patients after IVF failure. The ACA-positive patients accounted for 0.86% of all IVF patients (34/3955) and 2.51% of total ANA-positive IVF patients. Regardless of whether patients received conventional IVF (c-IVF) or intracytoplasmic sperm injection (ICSI), the ACA-positive group exhibited significant differences in oocyte maturity and fertilization compared to the ACA-negative group (both P<0.01). Moreover, the ACA-positive group had a decreased number of D3 suboptimal embryos and D3 optimal embryos (both P<0.05). In 5 cases of ACA-positive patients who underwent ICSI cycles, the two pronucleus (2PN) rate did not increase compared to c-IVF cycles (P>0.05), and there was a decrease in the number of D3 high-quality embryos and D3 suboptimal embryos (both P<0.05). After 1-2 months of immuno-suppressant treatment, 12 ACA-positive patients underwent c-IVF/ICSI again, and there were no changes in egg retrieval and fertilization before and after medication (both P>0.05), but there was an improvement in the 2PN embryo cleavage rate (P<0.05). The number of embryos transferred was similar between the ACA-positive and negative groups, but the ACA-positive group had significantly lower embryo implantation rate and clinical pregnancy rate compared to the ACA-negative group (both P<0.05), with no significant differences in the miscarriage rate between the two groups (P>0.05). Twenty-seven ACA-positive patients attempted natural conception or artificial insemination after IVF failure, resulting in a total of 7 cases of clinical pregnancy. Serum ACA positivity may disrupt oocyte maturation and normal fertilization processes, with no improvement observed with ICSI and immunosuppressant use. However, ACA-positive patients may still achieve natural pregnancy.

Untangling the relationship between smoking and systemic sclerosis: an analysis of the EUSTAR cohort

ObjectivesTo untangle the association between smoking and systemic sclerosis (SSc).MethodsIn the European Scleroderma Trials and Research cohort, the autoantibody status was compared between ever-smokers and never-smokers. Time until disease progression...

Prognostic value of anti-IFI16 autoantibodies in pulmonary arterial hypertension and mortality in patients with systemic sclerosis

ObjectivesTo determine the diagnostic value of anti-interferon gamma inducible protein 16 (IFI16) autoantibodies in systemic sclerosis (SSc) patients negative for all tested SSc-specific autoantibodies (SSc-seronegative patients) and to evaluate the clinical significance of these autoantibodies, whether isolated or in the presence of anti-centromere autoantibodies (ACA). MethodsOverall, 58 SSc-seronegative and 66 ACA-positive patients were included in the study. All patients were tested for anti-IFI16 autoantibodies by an in-house direct ELISA. Associations between clinical parameters and anti-IFI16 autoantibodies were analysed. ResultsOverall, 17.2% of SSc-seronegative and 39.4% of ACA-positive patients were positive for anti-IFI16 autoantibodies. Anti-IFI16 autoantibodies were found only in patients within the limited cutaneous SSc (lcSSc) subset. A positive association between anti-IFI16 positivity and isolated pulmonary arterial hypertension (PAH) was found (odds ratio [OR]=5.07; p=0.014) even after adjusting for ACA status (OR=4.99; p=0.019). Anti-IFI16-positive patients were found to have poorer overall survival than negative patients (p=0.032). Cumulative survival rates at 10, 20 and 30 years were 96.9%, 92.5% and 68.7% for anti-IFI16-positive patients vs. 98.8%, 97.0% and 90.3% for anti-IFI16-negative-patients, respectively. Anti-IFI16-positive patients also had worse overall survival than anti-IFI16-negative patients after adjusting for ACA status in the multivariate Cox analysis (hazard ratio [HR]=3.21; p=0.043). ConclusionAnti-IFI16 autoantibodies were associated with isolated PAH and poorer overall survival. Anti-IFI16 autoantibodies could be used as a supplementary marker of lcSSc in SSc-seronegative patients and for identifying ACA-positive patients with worse clinical outcome.

Anti-topoisomerase, but not anti-centromere B cell responses in systemic sclerosis display active, Ig-secreting cells associated with lung fibrosis

ObjectivesAlmost all patients with systemic sclerosis (SSc) harbour autoantibodies. Anti-topoisomerase antibodies (ATA) and anti-centromere antibodies (ACA) are most prevalent and associate with distinct clinical phenotypes. B cell responses underlying these...

Clinical Risk Factors for Dysphagia and Esophageal Dysmotility in Systemic Sclerosis.

Systemic sclerosis (SSc) is often associated with dysphagia and esophageal dysmotility; however, only a few clinical studies on this topic have been conducted. Patients with SSc who underwent swallowing examinations and esophagography at our institution between 2010 and 2022 were included. A retrospective evaluation of the patients' backgrounds, autoantibody positivity, swallowing function, and esophageal motility was performed using medical charts. The association between dysphagia and esophageal dysmotility in patients with SSc and respective risk factors was investigated. Data were collected from 50 patients. Anti-topoisomerase I antibodies (ATA) and anti-centromere antibodies (ACA) were detected in 21 (42%) and 11 (22%) patients, respectively. Dysphagia was present in 13 patients (26%), and esophageal dysmotility in 34 patients (68%). ATA-positive patients had a higher risk for dysphagia (p = 0.027); ACA-positive patients had a significantly lower risk (p = 0.046). Older age and laryngeal sensory deficits were identified as risk factors for dysphagia; however, no risk factors for esophageal dysmotility were identified. No correlation was found between dysphagia and esophageal dysmotility. Esophageal dysmotility is more common in patients with SSc than in those with dysphagia. Autoantibodies can be predictors of dysphagia, and dysphagia must be carefully considered in ATA-positive and elderly patients with SSc.

Comprehensive autoantibody profiles in systemic sclerosis: Clinical cluster analysis.

Systemic sclerosis (SSc) belongs to the group of connective tissue diseases and is associated with the occurrence of disease-specific autoantibodies. Although it is still controversial whether these antibodies contribute to pathogenesis, there are new insights into the development of these specific antibodies and their possible pathophysiological properties. Interestingly, they are associated with specific clinical manifestations, but for some rarer antibodies this association is not fully clarified. The aim of this study is a comprehensive analysis of the serum autoantibody status in patients with SSc followed by correlation analyses of autoantibodies with the clinical course of the disease. Serum from SSc patients was analyzed using a line blot (EUROLINE, EUROIMMUN AG) for SSc-related autoantibodies. Autoantibodies to centromere, Topo-1, antimitochondrial antibodies (AMA) M2 subunit, angiotensin II type 1 receptors (AT1R) and endothelin-1 type-A-receptors (ETAR) were also determined by ELISA. We formed immunological clusters and used principal components analysis (PCA) to assign specific clinical characteristics to these clusters. A total of 372 SSc patients were included. 95.3% of the patients were antinuclear antibody positive and in 333 patients at least one SSc specific antibody could be detected. Four immunological clusters could be found by PCA. Centromere, Topo-1 and RP3 all formed own clusters, which are associated with distinct clinical phenotypes. We found that patients with an inverted phenotype, such as limited cutaneous SSc patients within the Topo-1 cluster show an increased risk for interstital lung disease compared to ACA positive patients. Anti-AT1R and anti-ETAR autoantibodies were measured in 176 SSc patients; no association with SSc disease manifestation was found. SSc patients with AMA-M2 antibodies showed an increased risk of cardiovascular events. In our in large cluster analysis, which included an extended autoantibody profile, we were able to show that serologic status of SSc patients provides important clues to disease manifestation, co-morbidities and complications. Line blot was a reliable technique to detect autoantibodies in SSc and detected rarer autoantibodies in 42% of our patients.

Anticentromere antibody positive patients with primary Sjögren's syndrome have distinctive clinical and immunological characteristics.

To investigate the clinical manifestations, immunological characteristics, circulating lymphocyte subsets and risk factors of anticentromere antibody (ACA) positive patients with primary Sjögren's syndrome (pSS). Data of 333 patients with newly diagnosed pSS were collected and analysed retrospectively. The demographic features, glandular dysfunction, extraglandular manifestations, laboratory data, peripheral blood lymphocyte profiles and serum cytokines were compared between ACA-positive and ACA-negative pSS patients. Logistic regression analysis was used to evaluate the association between ACA and pSS characteristics. The prevalence of ACA among pSS patients was 13.5%. ACA-positive pSS patients were older at diagnosis and had longer disease duration. Xerostomia, xerophthalmia, parotid enlargement, Raynaud's phenomenon (RP), lung and digestive system involvement were more common in ACA-positive group, whereas haematological involvement such as leukopenia was more common in the ACA-negative group. Less frequency of rheumatoid factor, hypergammaglobulinaemia, anti-SSA and anti-SSB positivity, as well as higher positivity rate of ANA were observed in ACA-positive pSS patients, who exhibited a lower ESSDAI. In addition, decreased B cells and elevated NK cells were found in ACA-positive patients. Multivariate analysis identified that disease duration longer than 5 years, parotid enlargement, normal immunoglobulin and the absence of anti-SSA antibody were risk factors of ACA-positive pSS. ACA positive pSS patients have distinctive clinical manifestations and less severe immunological features, present a lower disease activity and lower activation of the humoral immune system. Physicians should pay attention to RP, lung and liver involvement in this subset of pSS.

DOES ADMINISTRATION OF PREDNISOLONE TO ANTI-CENTROMERE ANTIBODY-POSITIVE PATIENTS IMPROVE OOCYTE MATURATION AND FERTILIZATION RATES AFTER OVUM PICKUP AND INTRACYTOPLASMIC SPERM INJECTION?

It has been reported that anti-nuclear antibody (ANA)-positive patients have a lower oocyte maturation rate after ovum pickup (OPU). In particular, patients with positive anti-centromere antibodies (ACA), a member of the ANA family, are more likely to have a lower oocyte maturation rate and abnormal fertilization rate. Previous reports showed that administration of prednisolone in ANA-positive patients improved intracytoplasmic sperm injection (ICSI) outcomes. However, its effects in ACA-positive patients are unknown.

P-766 Birth outcomes in Anti-centromere antibody (ACA) -positive patients treated with ART

Abstract Study question Does the presence of the ACA have any effect on pregnancy and birth? Summary answer Presence of ACA did not have an impact on pregnancy and birth parameters measured. What is known already We have previously shown that patients with high levels of anti-centromere antibody (ACA), one of the anti-nuclear antibodies (ANA), frequently have dispersion of chromosomes in the cytoplasm. Additionally, we reported that it was characterized by a low oocyte maturation rate as observed at ovum pick up, high multiple pronuclear formation after fertilization and a low pregnancy rate after embryo transfer. Thus, the effect of ACA on fertility is clear, but the impact following pregnancy establishment has not yet been reported. Therefore, we followed up on birth outcomes in ACA-positive patients treated with ART. Study design, size, duration 3379 patients who underwent ANA testing followed by embryo transfer between January 2014 and February 2020 and who gave birth including the results of single births with no abnormal or missing values for week and birth weight were analyzed. The subjects were classified into three groups: ANA-negative (without ACA or any other ANA), ACA-positive (with only ACA) and ANA-positive (with ANA but not ACA). Participants/materials, setting, methods We compared mean birth weight (full term), low weight birth infant (less than 2,500g) rate, sex ratio, congenital anomaly rate, preterm birth rate, cesarean section rate, and mean apgar score (AP) in the three groups. We treated “don't know” and “blank” for items other than week and birth weight as non-responses and missing values. Main results and the role of chance Of the 3379 cases for analysis, the group numbers were ANA-: 2465, ACA+: 21, ANA+: 893. The mean birth weights were 3099.6g, 3055.3g and 3088.5g respectively. In the 3 groups the rate of low birth weight infants were 8.7% (215/2465), 9.5% (2/21) and 9.2% (82/893), the sex ratio (male/female)-1.03 (1246/1212), 0.62 (8/13) and 0.93 (429/ 460), congenital anomaly rate 2.7% (67/2465), 4.8% (1/21), 3.2% (29/893), preterm birth rate 7.4% (86/2465), 4.8% (1/12), 6.7% (60/893), cesarean rate 40.0% (979/2448), 42.9% (9/21), 41.3% (367/888), and mean AP was 8.3, 8.2, and 8.3 respectively. There was no significant difference between the three groups in any of the measured items. Limitations, reasons for caution This study was conducted at a single institution, and only the results of those who responded to the birth survey questionnaire were analyzed. Because of the small number of patients in the ACA group, continued follow-up is considered necessary. Wider implications of the findings It was shown that ACA strongly affects maternal fertility, but seems to have no effect on birth parameters. However we will continue to follow up with further long-term prognostic studies. Trial registration number not applicable

Clinical and laboratory characteristics of lymphoproliferative diseases in primary Sjogren's syndrome associated with anticentromere antibodies

Purpose of the study. To study the characteristics and frequency of lymphomas in patients with Sjogren's disease (SD) and anticentromere antibodies (ACA); to evaluate the predictors of the development of lymphoproliferative diseases (LPD) in this group of patients. Material and methods. Over the period from 1998 till 2019, 131 ACA-positive patients were under medical supervision at the Research Institute of Rheumatology named after Nasonova V.A. Isolated SD was diagnosed in 82 patients (62.6%), isolated limited form of SSc — in 12 patients (9.2%), combination of SD and limited form of SSc — in 37 patients (28.2%). Lymphoproliferative diseases (LPD) were diagnosed in 20 ACA-positive patients: in 15 — with SD, in 5 — with SD and SSc; no lymphomas were found in the group of patients with isolated SSc. All lymphomas were diagnosed on the basis of histological, immunohistochemical and PCR examination with of B-cell clonality determination in the tissue, and were classified on the base of haematopoietic and lymphoid tissue tumors classification by the World Health Organization. Further analysis included 15 ACA-positive patients with isolated SD and lymphomas. Results. In our study, 18.3% of patients with isolated ACA-positive SD were diagnosed with LPD, represented by MALT lymphomas of the salivary glands (subsequent transformation into aggressive diffuse large B-cell lymphoma (DLBCL) was noted in one patient) in most cases. The course of SD before the diagnosis of LPD was characterized by a gradual progression of dental manifestations of SD with the development of late stages of parenchymal parotitis, severe xerostomia, and significant enlargement of the salivary glands with a minimum number of systemic manifestations of the disease. Significant enlargement of salivary glands, severe infiltration of minor salivary glands, severe xerostomia, decreased level of C4-complement component, monoclonal secretion, low content of CD19+B-cells in peripheral blood, positive B-cell clonality in biopsy material were the main signs of LPD in this study. When diagnosing MALT lymphomas, a focal damage of the salivary glands with no signs of dissemination, no symptoms of B-cell intoxication, and minimal changes in laboratory assessment were found in patients with ACA-positive SD. Conclusion. The natural course of ACA-positive SD and the absence of pathogenetic therapy at an early stage contribute to the development of salivary gland lymphomas in the first 10 years of the disease. Persistent enlargement of the salivary glands in SD, especially in the presence of other predictors of lymphoproliferation, is a direct indication for biopsy followed by the research to exclude the presence of lymphoma.

The characteristics of clinical laboratory indicators in anticardiolipin antibody positive cerebral infarction patients

• ACA positive patients had abnormal coagulation indices and blood lipids factor. • ACA positive patients had abnormal myocardial indices levels. • ACA positive patients had abnormal HCY, VB12 and folate levels. • .ACA positive patients were inclined to have recurrent thrombosis.

Ultrasonographic characteristics of major salivary glands in anti-centromere antibody-positive primary Sjögren's syndrome.

To investigate salivary gland ultrasonography (SGUS) findings in primary Sjögren's syndrome (pSS) patients positive for the anti-centromere antibody (ACA) and compare these with those in ACA-negative pSS patients. We analyzed demographic, clinical, laboratory, and SGUS data of pSS patients who fulfilled the 2002 American-European Consensus Group classification criteria for pSS. SGUS findings of four major salivary glands (bilateral parotid and submandibular glands) were scored in five categories and compared between ACA-positive and ACA-negative pSS patients. Linear regression analysis was performed to elucidate the factors associated with SGUS score. In total, 121 pSS patients were enrolled (19, ACA-positive). The ACA-positive patients were older (67.0 vs 58.0 years, P = 0.028), whereas anti-Ro/SSA and anti-La/SSB positivity was more prevalent in the ACA-negative group (89.2% vs 21.1%, P < 0.001, and 47.1% vs 10.5%, P = 0.007, respectively). The total SGUS and hypoechoic area scores were lower in ACA-positive patients (16.0 vs 23.0, P = 0.027, and 4.0 vs 7.0, P = 0.004, respectively). In univariate regression analysis, being positive for unstimulated salivary flow rate (USFR < 1.5 ml/15 min), anti-Ro/SSA, and rheumatoid factor were positively associated whereas ACA positivity was negatively associated with the SGUS score. In multivariate regression analysis, being positive for USFR, anti-Ro/SSA, and rheumatoid factor showed significant association with the SGUS score. ACA-positive pSS patients showed a lower SGUS score than ACA-negative patients, which was especially prominent in the hypoechoic area component.

Anticentromere Antibody Levels and Isotypes and the Development of Systemic Sclerosis.

ObjectiveLittle is known on the disease course of very early systemic sclerosis (SSc). Among the information yet to be elucidated is whether anticentromere antibody (ACA) isotype levels can serve as biomarkers for future SSc development and for organ involvement. This study was undertaken to evaluate whether IgG, IgM, and IgA ACA levels in IgG ACA–positive patients are associated with disease severity and/or progression from very early SSc to definite SSc.MethodsIgG ACA–positive patients from 5 different cohorts who had very early SSc or SSc fulfilling the American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) 2013 criteria were included. A diagnosis of very early SSc was based on the presence of IgG ACAs and Raynaud’s phenomenon, and/or puffy fingers and/or abnormal nailfold capillaroscopy, but not fulfilling the ACR/EULAR 2013 criteria for SSc. Multivariable regression analyses were performed to determine the association between baseline ACA isotype levels and progression to definite SSc with organ involvement.ResultsSix hundred twenty‐five IgG ACA–positive patients were included, of whom 138 (22%) fulfilled the criteria for very early SSc and 487 (78%) had definite SSc. Levels of IgG ACAs (odds ratio 2.5 [95% confidence interval 1.8–3.7]) and IgM ACAs (odds ratio 1.8 [95% confidence interval 1.3–2.3]) were significantly higher in patients with definite SSc. Of 115 patients with very early SSc with follow‐up, progression to definite SSc occurred within 5 years in 48 (42%). Progression to definite SSc was associated with higher IgG ACA levels at baseline (odds ratio 4.3 [95% confidence interval 1.7–10.7]).ConclusionACA isotype levels may serve as biomarkers to identify patients with very early SSc who are at risk for disease progression to definite SSc.

P–354 Analysis of pregnancy and miscarriage rates in anti-centromere antibodies (ACA)-positive patients treated with ART

Abstract Study question Do ACA have an effect on pregnancy and miscarriage rates of human embryos? Summary answer The present results suggest that in ACA-positive cases, the pregnancy rate per transfer was significantly lower, although the miscarriage rate was not affected. What is known already We have previously shown that patients with high levels of anti-centromere antibody (ACA), (one of the anti-nuclear antibodies (ANA)), frequently have dispersal of the female chromosomes in the cytoplasm. Additionally, we reported that the clinical outcome was characterized by a low oocyte maturation rate following ovum pick up and high multiple pronuclear formation rate after fertilization. However, the post-implantation course of embryos with ACA-positive cases has not yet been reported. Therefore, in this study, we analyzed the pregnancy and miscarriage rates in ACA-positive patients treated with Assisted Reproductive Technologies (ART). Study design, size, duration 6581 patients who underwent embryo transfer after antinuclear antibody testing between January 2014 and February 2020 were included in the analysis. Participants/materials, setting, methods The subjects were classified into three groups: ANA-negative (without ACA or any other ANA), ACA-positive (with only ACA) and ANA-positive (with ANA but not ACA). The cycle in which the gestational sac was confirmed was considered a positive pregnancy. The pregnancy and miscarriage rates were compared among the groups using “Ryan Test” for statistical analysis. Main results and the role of chance Of the 6581 eligible cases, the incidence of antinuclear antibody were 71.3% (4695/6581; ANA-negative), 0.9% (61/6581; ACA-positive) and 27.7% (1825/6581; ANA-positive). The pregnancy rates based on the total number of embryo transfer cycles for each were ANA-negative: 31.5% (5283/16792), ACA-positive: 17.6% (41/233), and ANA-positive: 32.4% (1891/5833). The pregnancy rates were significantly lower in the ACA-positive group than in the other groups. The miscarriage rate was 29.4% (1553/5283) in ANA-negative, 31.7% (13/41) in ACA-positive, and 28.0% (529/1891) in ANA-positive, with no significant difference between the three groups. Limitations, reasons for caution Retrospective analysis Wider implications of the findings: ACA-positive patients may benefit from a treatment strategy to increase the absolute number of oocytes by obtained in order to increase the chances of normal fertilization and attainment of implantation. Trial registration number none

Comprehensive analysis of the major histocompatibility complex in systemic sclerosis identifies differential HLA associations by clinical and serological subtypes

ObjectiveThe greatest genetic effect reported for systemic sclerosis (SSc) lies in the major histocompatibility complex (MHC) locus. Leveraging the largest SSc genome-wide association study, we aimed to fine-map this region...

Changes of Serum IgG Glycosylation Patterns in Primary Biliary Cholangitis Patients.

ObjectivePrimary biliary cholangitis (PBC) is an autoimmune cholestatic liver disease whose diagnosis is based significantly on autoantibody detection. This study aims to investigate the glycosylation profile of serum IgG in PBC patients using high-throughput lectin microarrays technology.MethodLectin microarray containing 56 lectins was used to detect and analyze the expression of serum IgG glycosylation in 99 PBC patients, 70 disease controls (DCs), and 38 healthy controls (HCs). Significant differences in PBC from control groups as well as across PBC subgroups positive for various autoantibodies were explored and verified by lectin blot technique.ResultsLectin microarray detection revealed that compared to DC and HC groups, the specific glycan level of serum IgG sialic acid in PBC patients was increased. For each PBC subgroup, glycan levels of IgG mannose and galactose were decreased in AMA-M2 positive PBC patients compared to the AMA-M2 negative group. IgG N-Acetylgalactosamine (GalNAc) and fucose were decreased in anti-sp100 positive patients. IgG galactose was increased in anti-gp210 positive patients. IgG mannose was decreased in ACA-positive patients. Although the difference in overall sialic acid level was not observed using lectin blot, all results among the above PBC subgroups were consistent with the results of the technique.ConclusionLectin microarray is an effective and reliable technique for analyzing glycan structure. PBC patients positive for different autoantibody exhibits distinct glycan profile. Altered levels of glycosylation may be related to the occurrence and development of the disease, which could provide a direction for new biomarker identification.

Autoimmune liver damage in patients with primary Sjogren's syndrome associated with anticentromeric antibodies

Objective: to determine the frequency, spectrum and severity of liver affection in anti-centromere antibodies (ACA) positive patients with primary Sjogren's syndrome (pSS).Patients and methods. 119 ACA-positive patients with pSS were included in the study, 37 (31%) of them had signs of liver damage, 3 of these patients were excluded from the study (2 had cholelithiasis, 1 had viral hepatitis B). Signs of autoimmune liver damage were found in 34 (28.6%) patients, most of them were seropositive for antimitochondrial antibodies (AMA). The diagnosis of primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH) was established according to the recommendations of the American Association for the Study of Liver Diseases, the Russian Gastroenterological Association and the Russian Society for the Study of the Liver. In 5 (14.7%) patients the cause of cholestasis remained unspecified.Results and discussion. AMA were found in 73.5% of patients, elevated serum IgM levels – in 57.6%. Clinically liver damage in most cases was characterized by an asymptomatic, slowly progressive course without a dramatic increase of symptoms over time. Liver cirrhosis was found in 14.7% of patients. According to clinical, laboratory and morphological manifestations, PBC was diagnosed in 21 patients, 4 of them also had a cross syndrome with AIH. AMA-negative PBC was found in 3 patients and isolated AIH – in 1. In most cases, histological stage I of PBC was detected. During follow-up, median of 7 years (range from 2 to 15 years), in 7 patients with stage I PBC and in 7 AMA-positive patients without functional liver disorders no clinical, laboratory or instrumental progression of liver damage was noted. In this regard, it was suggested that these patients have epitheliitis of the biliary ducts as manifestation of glandular affection in pSS, and not true PBC.Conclusion. Autoimmune liver lesions are detected in 28.6% of ACA-positive patients with pSS, most (41.2%) of them develop epitheliitis of the biliary ducts as pSS manifestation or a combination of pSS with PBC (with the same frequency), less often PBC / AIH cross syndrome is diagnosed. PBC / pSS-related epitheliitis of the biliary ducts in ACA-positive patients is characterized by a slowly progressive asymptomatic course in most cases and rarely leads to the development of liver cirrhosis.