Single-cell transcriptome analyses reveal disturbed decidual homoeostasis in obstetric antiphospholipid syndrome.

OBJECTIVES: Obstetric antiphospholipid syndrome (OAPS) is an autoimmune disease characterised by the presence of antiphospholipid antibodies in circulation and pathological pregnancy. However, the pathogenesis of OAPS remains unknown. We aimed to reveal cellular compositions and molecular features of decidual cells involved in the development of OAPS using single-cell RNA sequencing (scRNA-seq). METHODS: We performed unbiased scRNA-seq analysis on the first-trimester decidua from five OAPS patients and five healthy controls (HCs), followed by validations with flow cytometry, immunohistochemical staining and immunofluorescence in a larger cohort. Serum chemokines and cytokines were measured by using ELISA. RESULTS: A higher ratio of macrophages but a lower ratio of decidual natural killer (dNK) cells was found in decidua from OAPS compared with HCs. Vascular endothelial cells shrinked in OAPS decidua while having upregulated chemokine expression and conspicuous responses to IFN-γ and TNF-α. Macrophages in OAPS had stronger phagocytosis function, complement activation signals and relied more on glycolysis. dNK cells were more activated in OAPS and had enhanced cytotoxicity and IFN-γ production. Downregulation of granules in OAPS dNK cells could be associated with suppressed glycolysis. Moreover, stromal cells had a prosenescent state with weakened immune surveillance for senescent cells in OAPS. In addition, the cellular interactions between decidual immune cells and those of immune cells with non-immune cells under disease state were altered, especially through chemokines, IFN-γ and TNF-α. CONCLUSION: This study provided a comprehensive decidual cell landscape and identified aberrant decidual microenvironment in OAPS, providing some potential therapeutic targets for this disease.

Application of T-cell receptor repertoire as a novel monitor in dynamic tracking and assessment: A cohort-study based on RA patients.

T-cell receptor repertoire (TCRR) sequencing has been widely applied in many fields as a novel tool. This study explored characteristics of TCRR in detail with a cohort of 598 rheumatoid arthritis (RA) patients before and after anti-rheumatic treatments. We highlighted the abnormal TCRR distribution in RA characterized by decreased diversity and increased proportion of hyperexpanded clones (HECs), which was potentially attributed to skewed usage of global V/J segments but not a few certain ones. Enriched motifs analysis in RA community demonstrated the huge heterogeneity of CDR3 sequences, so that individual factors are strongly recommended to be taken into consideration when it comes to clinical application of TCRR. Disease-modifying antirheumatic drugs (DMARDs) can regulate immune system through recovery of TCRR richness to relieve symptoms. Remarkably, sensitive gene profile and advantageous gene profile were identified in this study as new biomarkers for different DMARDs regimens.

Interleukin-1ß as clinically predictive risk marker for recurrent pregnancy loss in women positive for antinuclear antibody.

AIMS: Antinuclear antibody (ANA) was found to be associated with recurrent pregnancy loss (RPL). This study was designed to explore the immunological predictive indicators of RPL in women with positive ANA. METHODS: A retrospective case-control study in a university hospital from March 2020 to January 2021 was performed, including 56 cases of women with RPL and 56 controls matched for age, all of which were positive for ANA. Levels of cytokines, lymphocyte subsets, immune globulin and complement in peripheral blood among two groups were compared. Statistical analyses in this study were performed using SPSS 25.0. RESULTS: The level of IL-1ß was higher in RPL women compared with controls according to univariable analysis and multivariable regression logistic analysis (7.67 [5.86-11.35] vs 5.00 [5.00-5.00], P = .000). After the cut-off value of IL-1ß was set as 5.66 pg/mL, the prevalence of RPL was significantly elevated in the high IL-1ß group as compared with the low IL-1ß group (P < .05). The sensitivity and specificity of IL-1ß predicting RPL in ANA-positive women were 76.8% and 91.1%, respectively. CONCLUSION: Increased IL-1ß may play roles in the occurrence of RPL among women with positive ANA. The level of the IL-1ß has the potential to be a predictive indicator of RPL in women with positive ANA.

Combined Mutation of the GATA2 Gene and STAT5B Gene in a Patient with Hypogammaglobulinemia and Autoimmunity.

Antibody deficiency is a type of primary immunodeficiency that often manifests as primary hypogammaglobulinemia, with or without repeated infections. Although primary immunodeficiency appears to be contrary to autoimmunity, they usually occur simultaneously, and the specific pathogenesis remains unknown. We herein describe an adult patient with autoimmune manifestations and recurrent infections. The case was characterized by a sustained decrease in serum immunoglobulin A, accompanied by decreased T lymphocytes, B lymphocytes, monocytes, and platelets in the peripheral blood and the presence of antinuclear and anti-SSA antibodies. Whole-exome sequencing for the patient revealed two spontaneous mutations in GATA2 (c.1084C>T) and STAT5B (c.1924A>C). This case report provides evidence that mutations in the GATA2 and STAT5B genes may be pathogenic in primary immunodeficiency and provides genetic evidence for the possible pathogenesis of primary immunodeficiency with autoimmune symptoms. However, further studies are needed to confirm the causal relationship.

Inhibitory role of long non-coding RNA OIP5-AS1 in rheumatoid arthritis progression through the microRNA-448-paraoxonase 1-toll-like receptor 3-nuclear factor κB axis.

NEW FINDINGS: What is the central question of this study? What are the functions of long non-coding (lnc) RNA OIP5-AS1 in development of rheumatoid arthritis inflammation and what is the molecular mechanism? What is the main finding and its importance? LncRNA OIP5-AS1 mitigates rheumatoid arthritis progression through the competitive endogenous RNA network involving the miR-448-paraoxonase 1 axis and through the inactivation of the toll-like receptor 3-nuclear factor κB signalling pathway. This study may offer new ideas for molecularly based control of rheumatoid arthritis. ABSTRACT: Rheumatoid arthritis (RA) is an autoimmune disorder with dysregulation of long non-coding RNAs (lncRNAs) possibly involved. This study aimed to inquire into the roles of lncRNA OIP5-AS1 in RA progression. A rat model of RA was induced. Overexpression of OIP5-AS1 was introduced in the model rats, and the changes in paw swelling, RA severity and the inflammatory factors interleukin (IL)-1ß, IL-10, IL-6 and tumour necrosis factor α were measured. Fibroblast-like synoviocytes (FLSs) from RA patients were collected for in vitro experiments. A gain- and loss-of function study of OIP5-AS1, miR-448 and paraoxonase 1 (PON1) was performed to explore their roles in RA-FLS growth, apoptosis and inflammation. A toll-like receptor 3 (TLR3)-specific agonist, polyinosine-polycytidylic acid, or a nuclear factor κB (NF-κB)-specific antagonist, QNZ, was administrated in RA-FLSs. Consequently, overexpression of OIP5-AS1 reduced the symptom severity and the levels of inflammatory factors in RA rats. OIP5-AS1 could bind to miR-448 to up-regulate PON1 expression. Further overexpression of miR-448 reversed the effects of OIP5-AS1, while overexpression of PON1 inhibited RA-FLS growth and inflammation. In addition, TLR3 activation promoted RA progression. To conclude, this study evidenced that lncRNA OIP5-AS1 may mitigate RA progression through the miR-448-PON1 axis and through the inactivation of the TLR3-NF-κB signalling pathway.

Genetic characteristics of common variable immunodeficiency patients with autoimmunity.

Background: The pathogenesis of common variable immunodeficiency disorder (CVID) is complex, especially when combined with autoimmunity. Genetic factors may be potential explanations for this complex situation, and whole genome sequencing (WGS) provide the basis for this potential. Methods: Genetic information of patients with CVID with autoimmunity, together with their first-degree relatives, was collected through WGS. The association between genetic factors and clinical phenotypes was studied using genetic analysis strategies such as sporadic and pedigree. Results: We collected 42 blood samples for WGS (16 CVID patients and 26 first-degree relatives of healthy controls). Through pedigree, sporadic screening strategies and low-frequency deleterious screening of rare diseases, we obtained 9,148 mutation sites, including 8,171 single-nucleotide variants (SNVs) and 977 Insertion-deletions (InDels). Finally, we obtained a total of 28 candidate genes (32 loci), of which the most common mutant was LRBA. The most common autoimmunity in the 16 patients was systematic lupus erythematosis. Through KEGG pathway enrichment, we identified the top ten signaling pathways, including "primary immunodeficiency", "JAK-STAT signaling pathway", and "T-cell receptor signaling pathway". We used PyMOL to predict and analyse the three-dimensional protein structures of the NFKB1, RAG1, TIRAP, NCF2, and MYB genes. In addition, we constructed a PPI network by combining candidate mutants with genes associated with CVID in the OMIM database via the STRING database. Conclusion: The genetic background of CVID includes not only monogenic origins but also oligogenic effects. Our study showed that immunodeficiency and autoimmunity may overlap in genetic backgrounds. Clinical Trial Registration: identifier ChiCTR2100044035.

Single-cell transcriptome analysis and protein profiling reveal broad immune system activation in IgG4-related disease.

IgG4-related disease (IgG4-RD) is a systemic autoimmune disease with unclear pathogenesis. We performed single-cell RNA-seq and surface proteome analyses on 61,379 PBMCs from 9 treatment-naive IgG4-RD patients and 7 age- and sex-matched healthy controls. Integrative analyses were performed for altered gene expression in IgG4-RD, and flow cytometry and immunofluorescence were used for validation. We observed expansion of plasmablasts with enhanced protein processing and activation, which correlated with the number of involved organs in IgG4-RD. Increased proportions of CD4+ cytotoxic T lymphocytes (CTLs), CD8+ CTLs-GNLY (granulysin), and γδT cells with enhanced chemotaxis and cytotoxicity but with suppressed inhibitory receptors characterize IgG4-RD. Prominent infiltration of lymphocytes with distinct compositions were found in different organs of IgG4-RD patients. Transcription factors (TFs), including PRDM1/XBP1 and RUNX3, were upregulated in IgG4-RD, promoting the differentiation of plasmablasts and CTLs, respectively. Monocytes in IgG4-RD have stronger expression of genes related to cell adhesion and chemotaxis, which may give rise to profibrotic macrophages in lesions. The gene activation pattern in peripheral immune cells indicated activation of multiple interaction pathways between cell types, in part through chemokines or growth factors and their receptors. Specific upregulation of TFs and expansion of plasmablasts and CTLs may be involved in the pathogenesis of IgG4-RD, and each of these populations are candidate targets for therapeutic interventions in this disease.

Alteration of Gut Microbiota in Individuals at High-Risk for Rheumatoid Arthritis Associated With Disturbed Metabolome and the Initiation of Arthritis Through the Triggering of Mucosal Immunity Imbalance.

OBJECTIVE: In this study, we aimed to decipher the gut microbiome (GM) and serum metabolic characteristic of individuals at high risk for rheumatoid arthritis (RA) and to investigate the causative effect of GM on the mucosal immune system and its involvement in the pathogenesis of arthritis. METHODS: Fecal samples were collected from 38 healthy individuals and 53 high-risk RA individuals with anti-citrullinated protein antibody (ACPA) positivity (Pre-RA), 12 of 53 Pre-RA individuals developed RA within 5 years of follow-up. The differences in intestinal microbial composition between the healthy controls and Pre-RA individuals or among Pre-RA subgroups were identified by 16S ribosomal RNA sequencing. The serum metabolite profile and its correlation with GM were also explored. Moreover, antibiotic-pretreated mice that received GM from the healthy control or Pre-RA groups were then evaluated for intestinal permeability, inflammatory cytokines, and immune cell populations. Collagen-induced arthritis (CIA) was also applied to test the effect of fecal microbiota transplantation (FMT) from Pre-RA individuals on arthritis severity in mice. RESULTS: Stool microbial diversity was lower in Pre-RA individuals than in healthy controls. The bacterial community structure and function significantly differed between healthy controls and Pre-RA individuals. Although there were differences to some extent in the bacterial abundance among the Pre-RA subgroups, no robust functional differences were observed. The metabolites in the serum of the Pre-RA group were dramatically different from those in the healthy controls group, with KEGG pathway enrichment of amino acid and lipid metabolism. Moreover, intestinal bacteria from the Pre-RA group increased intestinal permeability in FMT mice and zonula occludens-1 expression in the small intestine and Caco-2 cells. Moreover, Th17 cells in the mesenteric lymph nodes and Peyer's patches were also increased in mice receiving Pre-RA feces compared to healthy controls. The changes in intestinal permeability and Th17-cell activation prior to arthritis induction enhanced CIA severity in PreRA-FMT mice compared with HC-FMT mice. CONCLUSION: Gut microbial dysbiosis and metabolome alterations already occur in individuals at high risk for RA. FMT from preclinical individuals triggers intestinal barrier dysfunction and changes mucosal immunity, further contributing to the development of arthritis.

Case report: IgG4-related intracranial lesions mimicking multiple sclerosis in a 14-year-old girl.

Objectives: IgG4-related disease (IgG4-RD) is distinguished by the infiltration of IgG4-positive plasma cells in a variety of tissues and organs. Even so, central nervous system lesions associated with IgG4-RD are scarce. We present a case of IgG4-related brain parenchymal lesions that mimics multiple sclerosis in a young girl. Methods: The patient was followed by our neurology and rheumatology teams. Clinical information was recorded, and the brain was screened using magnetic resonance imaging (MRI). During follow-up, we examined serum IgE, IgG and IgG4 and lymph node biopsy. Results: Here, we presented details of a 14-year-old Chinese girl suffering from diplopia, left eyelid ptosis, right facial numbness, and right lower limb weakness admitted to our institute. Brain MRI revealed multiple sclerosis-like lesions in the brain parenchyma and spinal cord. During the follow-up, she developed lymphadenopathy. Elevation of serum, IgG, IgG4 and IgE and lymph node biopsy favors a diagnosis of IgG4-RD. The patient had a good response to glucocorticoids and mycophenolate mofetil. The literature review summarized eight previously reported IgG4-RD involving brain parenchyma. Discussion: Our case expands the known age spectrum of IgG4-RD. The intracranial IgG4-RD is rare and could mimic multiple sclerosis. Careful examination and dynamic review of disease history are crucial in the differential diagnosis.

Clinical significance of T cell receptor repertoire in primary Sjogren's syndrome.

BACKGROUND: Primary Sjogren's syndrome (SS) is a chronic inflammatory disease with unknown aetiology. Although clonal expansion of autoreactive T cells has been identified in patients with SS, the clinical correlation of T-cell receptor (TCR) variance in SS remains unclear. METHODS: TCRß repertoire sequencing was performed on 260 SS patients with 3-6 months of follow-up in a cohort study to dynamically assess the characteristics of TCR diversity and their clinical significance. FINDINGS: We found that SS patients had lower TCR diversity, but higher frequency of public clones than healthy controls (HCs). Significant differences were identified in the usage of the variable (V) gene, joining (J) gene, and V-J pairing between SS and HCs. Eighteen SS-associated clones were identified, showing a high sensitivity and specificity for disease classification. TCR diversity was correlated with the presence of dental caries, thrombocytopenia, hepatocholangeitis, antinuclear antibody, anti-SSA/SSB, and hypergammaglobulinemia but not with disease course, number of relapses, arthritis, rheumatoid factor, hypocomplementemia or disease activity defined by SSDAI. During follow-up, the TCR abnormalities remained, represented by more altered V/J usage and higher frequencies of SS-associated clones. Among SS patients, the sensitive subgroup had increased TCR diversity after treatment. Eighty-five SS-sensitivity associated TCRs were identified and used for sensitivity classification by cross validation with high specificity and sensitivity. INTERPRETATION: These results demonstrate that the TCR repertoire could provide insights into the disease status and prognosis in SS and other autoimmune diseases. FUNDING: This study was funded by the National Key Research and Development Program of China (2016YFC0906201), Sichuan Science and Technology Program (2020YJ0223), and the 1·3·5 project for disciplines of excellence, West China Hospital, Sichuan University (ZYGD18015).

Gut Microbiome and Metabolites in Systemic Lupus Erythematosus: Link, Mechanisms and Intervention.

Systemic lupus erythematosus (SLE), often considered the prototype of autoimmune diseases, is characterized by over-activation of the autoimmune system with abnormal functions of innate and adaptive immune cells and the production of a large number of autoantibodies against nuclear components. Given the highly complex and heterogeneous nature of SLE, the pathogenesis of this disease remains incompletely understood and is presumed to involve both genetic and environmental factors. Currently, disturbance of the gut microbiota has emerged as a novel player involved in the pathogenesis of SLE. With in-depth research, the understanding of the intestinal bacteria-host interaction in SLE is much more comprehensive. Recent years have also seen an increase in metabolomics studies in SLE with the attempt to identify potential biomarkers for diagnosis or disease activity monitoring. An intricate relationship between gut microbiome changes and metabolic alterations could help explain the mechanisms by which gut bacteria play roles in the pathogenesis of SLE. Here, we review the role of microbiota dysbiosis in the aetiology of SLE and how intestinal microbiota interact with the host metabolism axis. A proposed treatment strategy for SLE based on gut microbiome (GM) regulation is also discussed in this review. Increasing our understanding of gut microbiota and their function in lupus will provide us with novel opportunities to develop effective and precise diagnostic strategies and to explore potential microbiota-based treatments for patients with lupus.

Prevalence of Sexual Dysfunction in People With Systemic Sclerosis and the Associated Risk Factors: A Systematic Review.

INTRODUCTION: The association between systemic sclerosis (SSc) and sexual dysfunction was controversial. AIM: To explore the impacts of SSc on sexual function, the prevalence of sexual dysfunction in patients with SSc and associated risk factors. METHODS: A systematic review of all published studies was performed. Studies exploring the association between SSc and sexual function were retrieved from PubMed, Web of Science, and EBSCO. All retrieved papers were selected according to the inclusion and exclusion criteria. MAIN OUTCOME MEASURE: The impacts of SSc on sexual function, the prevalence of sexual dysfunction in males and females with SSc and associated risk factors. RESULTS: A total 12 studies were included in this study. The prevalence of sexual dysfunction in SSc males and SSc females were 76.9-81.4% and 46.7-86.6%, respectively. But the direct impacts of SSc on sexual function were controversial. EULAR SSc activity score ≥3, the number of complications ≥2, and the presence of anticardiolipin antibody and anti U1 ribonucleoprotein antibody in males and resistive index (RI) and the systolic/diastolic (S/D) ratio of clitoral blood in females have potential to be SSc-specific risk factors for sexual dysfunction. CLINICAL IMPLICATIONS: Clinicians need to pay more attention to the impacts of SSc on sexual function of patients especially in those with risk factors. STRENGTHS & LIMITATIONS: Systematically explored the prevalence of sexual dysfunction in SSc males and females, and the risk factors of sexual dysfunction for SSc were explored innovatively. However, there were some limitations in included studies prevented exploring the impacts of SSc on sexual function deeply. CONCLUSION: Sexual dysfunction may be an important symptom of SSc, many risk factors may be associated with sexual dysfunction in males and females with SSc. Gao R, Qing P, Sun X, et al. Prevalence of Sexual Dysfunction in People With Systemic Sclerosis and the Associated Risk Factors: A Systematic Review. Sex Med 2021;9:100392.

IgG4-Related Disease With Tuberculosis: A Case Report and Retrospective Review of Patients in a Single Center.

Background: IgG4-related disease (IgG4-RD) is a recently recognized systemic fibro-inflammatory disease of unknown cause involving many organs including pancreas, salivary glands, and lymph nodes. Chronic tuberculosis (TB) infection has been reported in IgG4-RD, but the prevalence of TB infection has not been evaluated in IgG4-RD. Methods: Characterization of a patient with IgG4-RD by physical examination, laboratory tests, magnetic resonance imaging (MRI) and histological examination. TB infection was evaluated by medical history, radiological examinations, sputum examinations, tubercular skin test (TST) and interferon gamma (IFN-γ) release assay test (IGRA). Medical records of IgG4-RD patients were reviewed in our institute from February 2015 to September 2020 to explore the prevalence of TB infection in IgG4-RD. Results: We described a 40-year-old Chinese man presented with headache and diplopia. Physical examination revealed bitemporal hemianopsia and limited abduction of both eyes. MRI revealed uniformly enhancing mass overlying clivus with dural tail sign. Laboratory data revealed elevation of IgG4 (1.9g/L), and TB-IGRA demonstrated significantly elevated IFN-γ (414.21 pg/ml). The clivus lesion was subtotally removed and IgG4 was strongly positive on immunohistochemical staining. The diagnosis of IgG4-RD was established, and the patient received treatment of corticosteroids, methotrexate, and cyclophosphamide with isoniazid prophylaxis. Consequently, the mass shrank remarkably within 3 months. A similar concurrence of TB disease or latent TB infection (LTBI) and IgG4-RD was present in 17/47 (36.2%) patients in our institute. Conclusion: High frequency of TB/LTBI presented in patients with IgG4-RD. Patients with IgG4-RD and LTBI should be closely monitored for resurgence of TB. Whether TB represents a risk for IgG4-RD should be further investigated in prospective cohort.

Antiphospholipid antibodies and pregnancy outcome of assisted reproductive treatment: A systematic review and meta-analysis.

PROBLEM: Antiphospholipid antibodies (aPLs) are a group of autoantibodies associated with a variety of pregnancy complications, but the impact of aPL on the outcomes of assisted fertility treatment (ART) is controversial. This systematic review and meta-analysis were designed to explore the association between aPL and ART outcomes and to explore in which stages does aPL play a role. METHOD OF STUDY: PubMed and Cochrane database were systematically retrieved, and odds ratios (ORs) or risk ratios (RRs) with 95% confidence intervals (CIs) were calculated in a random-effect model or fixed-effect model according to the heterogenicity assessed by the Cochran Q and I2  statistic test. Of 246 records identified by the search, 10 case-control studies and 13 cohort studies that explored the association between aPL and in vitro fertilization (IVF) and/or intracytoplasmic sperm injection (ICSI) were analyzed. RESULTS: The results showed that aPL positive rate was higher in females who failed in IVF/ICSI than those who succeeded in IVF/ICSI (OR: 3.62, 95% CI: 1.95-6.74). This study also indicated that females positive for aPL have a higher miscarriage rate (RR: 1.68, 95% CI: 1.24-2.28) than those negative for aPL, but live birth rate, biochemical pregnancy rate, and clinical pregnancy rate were similar between two groups (RR: 1.01, 95% CI: 0.91-1.12; RR: 1.18, 95% CI: 0.57-2.43 and RR: 0.95, 95% CI: 0.80-1.13). CONCLUSIONS: There was higher aPL prevalence in females with adverse IVF/ICSI outcomes. It seems that aPL mainly affects the miscarriage rate, but has little effect on live birth rate, biochemical pregnancy rate, and clinical pregnancy rate. Routine detection of aPL before IVF/ICSI treatment is meaningful.

Oral Microbiota Perturbations Are Linked to High Risk for Rheumatoid Arthritis.

Oral microbial dysbiosis is known to increase susceptibility of an individual to develop rheumatoid arthritis (RA). Individuals at-risk of RA may undergo different phases of disease progression. In this study, we aim to investigate whether and whereby the oral microbiome communities alter prior to symptoms of RA. Seventy-nine saliva samples were collected from 29 high-risk individuals, who were positive for anti-citrullinated protein antibodies (ACPA) and have no clinical arthritis, 27 RA patients and 23 healthy controls (HCs). The salivary microbiome was examined using 16S ribosomal RNA gene sequencing. Alpha and beta diversity analysis and the linear discriminant analysis were applied to examine the bacterial diversity, community structure and discriminatory taxa between three groups, respectively. The correlation between salivary bacteria and autoantibodies were analyzed. In the "pre-clinical" stages, salivary microbial diversity was significantly reduced comparing to RA patients and HCs. In contrast to HCs, like RA patients, individuals at high-risk for RA showed a reduction in the abundance of genus Defluviitaleaceae_UCG-011 and the species Neisseria oralis, but an expansion of Prevotella_6. Unexpectedly, the relative abundance of Porphyromonas gingivalis, reported as opportunistic pathogens for RA development, was significantly decreased in high-risk individuals. Additionally, we identified four genera in the saliva from high-risk individuals positively correlated with serum ACPA titers, and the other two genera inversely displayed. In summary, we observed a characteristic compositional change of salivary microbes in individuals at high-risk for RA, suggesting that oral microbiota dysbiosis occurs in the "pre-clinical" stage of RA and are correlated with systemic autoimmune features.

Elevated levels of TL1A are associated with disease activity in patients with systemic sclerosis.

TL1A is a member of the TNF superfamily. It performs significantly in the pathogenesis of rheumatic and autoimmune diseases partly through regulating the Th17 pathway. The clinical implication of circulating TL1A in patients with systemic sclerosis (SSc) remains unclear, and correlation between TL1A and Th17-related cytokines in the pathogenesis of SSc needs to be discussed. We measured serum levels of TL1A and Th17-related cytokines by ELISA in 47 patients with SSc, 56 patients with SLE, and 53 healthy subjects, and investigated association of these cytokines with clinical manifestations and laboratory variables. TL1A in relation to Th17-related cytokines were examined. In addition, the transcript level of TL1A in peripheral blood mononuclear cells (PBMCs) was determined by real-time reverse transcription polymerase chain reaction (real-time PCR). Serum TL1A levels were higher in patients with SSc than in healthy controls (P = 0.001), but were lower compared with SLE patients (P = 0.004). Diffuse cutaneous SSc or limited cutaneous SSc patients reported elevated expression of TL1A than those in healthy controls (P = 0.002, P = 0.007). Patients with active disease showed significantly higher expression of TL1A when compared with less active disease (P = 0.014). SSc patients with arthritis, elevated IgG titer, ESR >30 mm/h, and CRP >5 mg/l displayed elevated expression of TL1A, respectively. Serum levels of IL-17 and IL-21 were increased in SSc patients compared with healthy controls and positively related to TL1A levels (r s = 0.373, P = 0.010; r s = 0.370, P = 0.011, respectively). Moreover, TL1A mRNA expression in PBMCs was significantly higher in patients with SSc compared with healthy controls (P < 0.001). TL1A may play a role in the development of SSc.