BACKGROUND: Primary Sjogren\'s syndrome (pSS) is a complex autoimmune disease featuring damage to salivary and lacrimal glands, with the possibility of manifestations across multiple organs. Antibody-producing B cells have long been appreciated to play a significant role in pSS pathogenesis, with a number of autoreactive antibody species having been identified to be elevated in pSS patients. While several studies have attempted to characterize the BCR repertoires of peripheral blood B cells in pSS patients, much remains unknown about the repertoire characteristics of gland-infiltrating B cells.
METHODS: Through paired scRNAseq and scBCRseq, we profiled the BCR repertoires of both infiltrating and circulating B cells in a small cohort of patients. We further utilize receptor reconstruction analyses to further investigate repertoire characteristics in a wider cohort of pSS patients previously profiled through RNAseq.
RESULTS: Via integrated BCR and transcriptome analysis of B cell clones, we generate a trajectory progression pattern for infiltrated memory B cells in pSS. We observe significant differences in BCR repertoires between the peripheral blood and labial gland B cells of pSS patients in terms of relative expansion, isotype usage, and BCR clustering. We further observe significant decreases in IgA2 isotype usage among pSS patient labial and parotid gland B cells these analyses relative to controls as well as a positive correlation between kappa/lambda light chain usage and clinical disease activity.
CONCLUSIONS: Through BCR repertoire analysis of pSS patient salivary glands, we identify a number of novel repertoire characteristics that may serve as useful indicators of clinical disease and disease activity. By collecting these BCR repertoires into an accessible database, we hope to also enable comparative analysis of patient repertoires in pSS and potentially other autoimmune disorders.

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To strengthen the understanding of rheumatic diseases (RDs) as the most common underlying conditions associated with acquired hemophilia (AH), a potentially fatal bleeding condition due to the development of autoantibodies or inhibitors to coagulation factor VIII, and rarely to factor IX, here we presented two cases of RDs associated AH to elucidate the disease progression, treatment, and prognosis. The presented 2 cases showed good responses to glucocorticoid (GC) and immunosuppressive agents. And then, a case-based systematic review was conducted to better understand the clinically practiced diagnosis and treatment of RDs associated AH. A total of 14 articles were included in the final literature review. All the identified 14 patients with underlying RDs and AH presented with bleeding symptoms, increased APTT, decreased FVIII activity, and positive FVIII inhibitors. Twelve of the 14 patients (85.7%) started an eradication of autoantibodies treatment with GC and immunosuppressive agents. Among which six patients achieved partial or complete remission, and four patients (28.6%) switched to Rituximab and responded well. Nine of the 14 patients received hemostasis therapy, including recombinant human FVIIa (rFVIIa). Two patients (14.3%) died due to mass bleeding and key organ failure. AH should be highly suspected in patients with RDs presenting spontaneous mucocutaneous or internal bleeding and an isolated prolonged APTT. Given the high morbidity of AH, it is important to facilitate efficient and proper management.

Objective: To explore the clinical features and conduct prognostic analysis about visual recovery and relapse of neuromyelitisoptica (NMO) spectrum disease (NMOSD) with sjogren syndrome (SS). Methods: A retrospective and prospective observational study was conducted.Between July 2013 and June 2016, 172 patients with NMOSD (NMOSD-non SS: 116/172, 67.4%; NMOSD-SS: 56/172, 32.6%) were assessed at Beijing Tongren Hospital, Capital Medical University, Beijing, China.The prognostic factors of NMOSD-SS patients were also analyzed. Results: As compared with NMOSD-non SS patients, NMOSD-SS patients had worse visual impairment (percentage of patients with visual acuity less than 0.1, 83.9% vs 69.8%, P<0.05), higher positive rate of SSA (92.9% vs 0.0%, P<0.05), higher proportion of dryness of mouth and eye (66.1% vs 5.2%, P<0.05) as well as higher percentage of reduced visual evoked potential (VEP) amplitude (60.7% vs 43.1%, P<0.05). NMOSD-SS patients had a significantly higher average year recurrent frequency (0.58 vs 0.53) and significantly shorter mean recurrence time (6.7 months vs 12.4 months, P<0.05). The results showed that recurrent eyes, the worst visual acuities of onset less than 0.1 were independent risk factors of visual impairment (visual activity <0.1), according to at least six months\' follow-up of all NMOSD-SS patients (OR=6.410 and 9.434, respectively, P<0.05). Meanwhile, immunosuppressive drugs were protective factors of relapse in NMOSD-SS patients (OR=0.107, P<0.05). Conclusions: NMOSD-SS patients have worse visual impairment, and they are more vulnerable to relapse than NMOSD-non SS patients, and the vision is lack of recovery for NMOSD-SS with recurrent eyes or the worst vision of onset less than 0.1.Immunosuppressive drugs can reduce the recurrence of NMOSD-SS relapse.
目的：观察合并干燥综合征的视神经脊髓炎谱系疾病(NMOSD-SS)的临床特征，分析其视力恢复、复发的预后因素。 方法：回顾性＋前瞻性观察性研究。对2013年7月至2016年6月首都医科大学附属北京同仁医院神经内科确诊的172例视神经脊髓炎谱系疾病(NMOSD)患者进行观察、随访，比较56例NMOSD-SS与116例NMOSD-非SS的临床及影像学特征，分析NMOSD-SS患者视力恢复、复发的预后因素。 结果： (1) NMOSD-SS较NMOSD-非SS患者最差视力<0.1的比例高(83.9%比69.8%，P<0.05)、SSA阳性率高(92.9%比0.0%, P<0.05)、眼干或口干比例高(66.1%比5.2%, P<0.05)、视觉诱发电位(VEP)波幅降低比例高(60.7%比43.1%，P<0.05)。(2)NMOSD-SS较NMOSD-非SS患者年复发率高(0.58比0.53)、复发时间短(中位数6.7个月比12.4个月，P<0.05)。(3)对所有NMOSD患者进行至少半年的随访，发现本次发病为复发眼、发病时最差视力<0.1为其视力恢复不良(视力<0.1)的危险因素(OR值分别为6.410、9.434，P<0.05)，而应用免疫抑制剂是防止NMOSD复发的保护因素(OR值0.107，P<0.05)。 结论： NMOSD-SS较NMOSD-非SS视力损害严重，且更容易复发，本次发病为复发眼、发病时最差视力<0.1的NMOSD-SS患者视力恢复不良，使用免疫抑制剂可减少NMOSD-SS复发概率。.

BACKGROUND: Mitotic spindle apparatus (MSA) antibodies are rare findings with undefined clinical significance in clinical research. We aimed at investigating the prevalence and clinical significance of anti-MSA antibodies in Chinese population.
METHODS: Between 2008 and 2013, a total of 180,180 patients were studied for the presence of anti-MSA antibodies. The clinical details and laboratory data of anti-MSA-positive patients were retrospectively collected and analyzed.
RESULTS: Of the 180,180 patients tested, 68,640 patients presented with positive antinuclear antibodies (ANAs, 38.10%), but only 32 patients with positive anti-MSA antibodies (0.018%). Diagnoses were established in 22 of 32 patients: 16 connective tissue diseases (CTDs), mainly Sjogren syndrome (SS, 5/16), rheumatoid arthritis (RA, 4/16), and systemic lupus erythematosus (SLE, 3/16), and 6 nonautoimmune conditions. The most frequent clinical symptoms of the anti-MSA-positive patients were arthralgia and eyes and mouth drying. Additionally, 70% of anti-MSA antibodies were not associated with other ANAs, however, when associated, the most frequent ANA was anti-SSA.
CONCLUSIONS: Anti-MSA antibodies have a low prevalence and female gender predominance. Anti-MSA antibodies are primarily associated with CTDs, mainly SS, RA, and SLE. The presence of anti-MSA antibodies might be the unique serological markers of the CTDs, especially when anti-SSA, SSB, and dsDNA antibodies are negative, or the level of RF is low.