The role of trimethoprim/sulfamethoxazole in preventing opportunistic infections in systemic lupus erythematosus patients receiving low-level immunosuppressive treatment: an open-label, randomized, controlled trial.

OBJECTIVE: Systemic lupus erythematosus (SLE) patients receiving immunosuppressive therapy are at risk for opportunistic infections (OIs), particularly Pneumocystis pneumonia (PCP). This study aimed to evaluate the effectiveness of trimethoprim/sulfamethoxazole (TMP/SMX) as primary prophylaxis against OIs and its adverse effects in SLE patients receiving low-level immunosuppressive treatment in a real-world setting. METHODS: This open-label randomized controlled trial enrolled SLE patients receiving low-level immunosuppressive treatment at Ramathibodi Hospital between May 2021 and December 2022. Patient demographics and relevant clinical data were collected. Participants were randomized 1:1 to receive TMP/SMX or no prophylaxis, with dose adjustments according to renal function. The incidences of TMP/SMX-sensitive OIs and adverse events were monitored for 12 months post-enrollment. RESULTS: The trial was terminated early due to a high rate of adverse drug reactions (ADRs) associated with TMP/SMX. In total, 138 SLE patients receiving low-level immunosuppressive treatment were enrolled. Most patients (98.4%) were in disease remission. No TMP/SMX-sensitive OIs were observed in either group during the 12-month follow-up period. Among individuals receiving TMP/SMX, 10/70 (14.3%) developed ADRs. Of these 10 patients, eight experienced grade 1 ADRs, and two had grade 3 ADRs; all declined to resume prophylaxis. There were no deaths in the study. CONCLUSIONS: During the 12-month follow-up period, no TMP/SMX-sensitive OIs occurred in SLE patients receiving low-level immunosuppressive therapy, suggesting that primary prophylaxis with TMP/SMX may not significantly benefit this population. The high rate of ADRs observed underscores the need for clinicians to carefully consider the risks and benefits of TMP/SMX prophylaxis in these patients.

Activation of circulating TFH17 cells associated with activated naive and double negative 2 B cell expansion, and disease activity in systemic lupus erythematosus patients.

BACKGROUND: Systemic lupus erythematosus (SLE) is the quintessential autoimmune disease, as it is characterized by hyperactivity of CD4+ T cells and subsequently drives lupus pathology. Follicular helper T (TFH) cells play an important role in B cell maturation and antibody production. However, which specific subset of cTFH cells drives B cell function and contributes to the development of anti-dsDNA antibodies and SLE pathogenesis remains unclear. METHODS: Peripheral blood mononuclear cells from SLE patients with inactive (n = 11) and active (n = 21) were used to determine and detect frequencies and phenotypes of circulating TFH cells (cTFH), memory cTFH, and B cell subsets. The correlations among cTFH cell subsets and phenotypes, B cell subsets, anti-dsDNA autoantibodies, and clinical parameters were analyzed. RESULTS: In subjects with active SLE, cTFH1 and cTFH17 cells were significantly expanded and activated. These expanded cTFH cells expressed memory phenotypes; cTFH1 cells were predominantly central memory (CM) type, while cTFH17 cells were largely effector memory (EM) type. Phenotyping B cell subsets in these patients showed increased frequencies of aNAV and DN2 B cells. Clinically, ICOS+ cTFH1, ICOS+ cTFH17 cells, and SLEDAI-2k scores were found to be correlated. Analysis of cTFH-B cell relationship revealed positive correlations among ICOS+ cTFH1 cells, aNAV B cells, and anti-dsDNA antibodies. Activation of ICOS+ cTFH17 cells was significantly related to the expansion of aNAV and DN2 B cells. The presence of CM cells in cTFH1 and cTFH17 subsets was correlated with aNAV and DN2 B cell frequencies. CONCLUSION: SLE cTFH cells were found to be polarized toward cTFH1 and cTFH17 cells; activation of these cTFH subsets was significantly associated with disease activity score, aNAV, DN2 B cell expansion, and anti-dsDNA antibody level. Thus, the interactions among cTFH1, cTFH17, and B cells likely contribute to the development of autoantibodies and the pathogenesis in SLE.

Impact of vitamin D supplementation on the clinical outcomes of COVID-19 pneumonia patients: a single-center randomized controlled trial.

BACKGROUND: Vitamin D supplementation for infectious diseases has been discussed, but its role in COVID-19 is unclear. Therefore, this study examined the clinical outcomes of COVID-19 pneumonia patients who received vitamin D supplementation. METHODS: This prospective, open-label, randomized controlled trial was conducted in a university hospital between July 2020 and March 2022. The inclusion criteria were patients aged ≥ 18 years with COVID-19 pneumonia patients. The patients were randomized into two groups: an intervention group receiving vitamin D supplementation (alfacalcidol, two mcg orally daily) until discharge and a control group. The clinical outcomes were pneumonia treatment duration, length of hospital stay, and change in pneumonia severity index between enrollment and discharge. Subgroup analysis was conducted for supplemental oxygen use, high-dose corticosteroid administration, evidence of lymphopenia, C-reactive protein concentration, and total serum vitamin D concentration. Adverse events were monitored. RESULTS: Two hundred ninety-four patients were recruited (147 per group). The two groups did not differ in pneumonia treatment duration to discharge (p = 0.788) or length of hospital stay (p = 0.614). The reduction in the pneumonia severity index between enrollment and discharge was more significant in the intervention group (p = 0.007); a significant decrease was also observed among patients who had C-reactive protein > 30 mg/L (p < 0.001). No adverse reactions were recorded. CONCLUSIONS: Adding active vitamin D to standard treatment may benefit COVID-19 pneumonia patients who require supplemental oxygen or high-dose corticosteroid therapy or who have high C-reactive protein concentrations (> 30 mg/L) upon treatment initiation. TRIAL REGISTRATION: Thai Clinical Trials Registry TCTR20210906005 (retrospectively registered, 6 September 2021).

Clinical Characteristics of Anti-Synthetase Syndrome and Variables Associated with Interstitial Lung Disease and Mortality: A Retrospective Cohort Study.

Anti-synthetase syndrome (ASS) is a rare autoimmune disease. Since the knowledge of ASS remains limited, we conducted the retrospective study aiming to describe clinical characteristics and identify variables associated with interstitial lung disease (ILD) and mortality among patients with ASS. Patients diagnosed with ASS from January 2013 to October 2022 were included. Patient demographics, clinical manifestations, myositis auto-antibody profiles, HRCT findings, and laboratory tests were collected. Variables associated with mortality risk and ILD were evaluated using the Cox proportional hazards model and the logistic regression model, respectively. A total of 82 patients with ASS were included. Clinical manifestations included arthritis (57%), Raynaud's phenomenon (32%), mechanic's hands (29%), fever (26%), and myositis (17%). The myositis auto-antibody profiles included anti-PL-7 (29%), anti-Jo-1 (27%), anti-EJ (17%), anti-PL-12 (16%), and anti-OJ (11%). ILD was observed in 64 patients (78%). Among patients with ILD, 21 initially presented with ILD before developing other ASS clinical manifestations, 29 simultaneously presented with ILD and other symptoms, and 14 had isolated ILD throughout follow-up. Overall, 6 patients presented with rapid-progressive ILD. With a median follow-up time of 2.5 years, mortality was observed in 10 patients (12.2%). Factors associated with mortality included increased lymphocyte counts (adjusted HR, 0.74; 95% CI, 0.61-0.91; p < 0.01), isolated ILD (adjusted HR, 9.59; 95% CI, 1.52-60.61; p = 0.02) and the presence of anti-Ro52 antibodies (adjusted HR, 0.14; 95% CI, 0.02-0.93; p = 0.04). Factors associated with ILD included age (adjusted OR, 1.10; 95% CI, 1.03-1.18; p = 0.01), presence of anti-Ro52 antibodies (adjusted OR, 17.92; 95% CI, 2.13-138.68; p = 0.01), and presence of arthritis (adjusted OR, 0.09; 95% CI, 0.01-0.75; p = 0.03). Our study demonstrated a favorable overall mortality rate among ASS patients.

Health related quality of life in anti interferon γ autoantibody associated immunodeficiency syndrome measured with EQ5D5L and SF36.

The anti-IFN-γ disease is a rare condition characterized by recurrent and persistent infections, potentially impacting the quality of life (QoL). However, comprehensive data on QoL in this population are lacking. This study aims to evaluate the QoL of Anti-IFN-γ patients compared to healthy control and explore potential differences in QoL between patients in the active and remission stages. A cross-sectional study design was conducted, recruiting 38 Anti-IFN-γ patients and 38 sex- and age-matched healthy controls. QoL assessment utilized the 5-level EuroQol-5 Dimension (EQ-5D-5L) and the 36-Item Short Form Health Survey (SF-36). The Anti-IFN-γ group had a mean age of 57.37 (± 10.32) years, with females comprising 60.53%. Among the Anti-IFN-γ patients, 55.26% were classified as having active disease. 63% of Anti-IFN-γ patients received Immunosuppressive treatments. Anti-IFN-γ disease exhibited a significant negative impact on HRQoL, as evidenced by lower utility scores in EQ-5D-5L and lower physical and mental component scores in SF-36 across various domains, including physical function, role physical, general health, bodily pain, social functioning, role emotion and mental health, compared to healthy controls. Additionally, patients in the active disease displayed lower scores in multiple domains, including bodily pain, general health, role emotion and mental health, and a lower utility score in EQ-5D-5L compared to patients in remission. The anti-IFN-γ disease significantly impairs the HRQoL of affected individuals compared to healthy controls. However, effective treatment leading to remission holds promise for improving the HRQoL of patients with Anti-IFN-γ disease.

Real world safety of CT-P10 (anti-CD 20 monoclonal antibodies biosimilar) in rheumatic and autoimmune diseases.

BACKGROUND: Rituximab (RTX), anti-CD 20 monoclonal antibodies, has been approved for many rheumatic and autoimmune diseases, the use of RTX is still limited due to financial constrain. Biosimilar RTX may increase access by offering patients a more affordable option, lead to improved patient outcomes. However, real-world data related to its immediate and short-term safety is scarce. This study aimed to evaluate the real-world immediate and short-term safety profiles of CT-P10, a biosimilar of Rituximab, in patients with rheumatic and autoimmune diseases. METHODS: This prospective study included patients diagnosed with rheumatic or autoimmune diseases, aged ≥ 18 years, who were treated with biosimilar RTX at Siriraj or Ramathibodi Hospital during February 2019 to May 2019. Patients were followed up through 6 months after the infusions. RESULTS: Of the 74 patients, with 124 infusions, 84% were females with mean age (SD) of 49.4 (15.7) years. The most common rheumatic and autoimmune disease included in this study was systemic lupus erythematosus (26%). All immediate adverse events (AEs) (15 out of 124 infusions) were mild requiring only symptomatic and supportive treatment. Short-term AEs included infection (N = 35), hematologic abnormalities (N = 33), chylous ascites (N = 1), and others (N = 10). Two deaths were related to serious bacterial and viral infection. Hematologic AEs comprised anemia (N = 5), neutropenia (N = 10), lymphopenia (N = 15), and thrombocytopenia (N = 3). CONCLUSION: In this real-world study, biosimilar RTX (CT-P10) has favorable immediate and short-term safety profiles. However, further studies with large sample size and long-term follow-up in real-world practice are still required to confirm the result.

CD4+ T-cell cooperation promoted pathogenic function of activated naïve B cells of patients with SLE.

OBJECTIVE: To explore cooperation between activated naïve (aNAV) B cells and CD4+ T cells in the pathogenesis of SLE through autoantibody production, T-cell differentiation and inflammatory cytokine secretion. METHODS: Peripheral blood mononuclear cell samples were obtained from 31 patients with SLE and used to characterise phenotype of aNAV B cells (n=14) and measured the phosphorylation of B-cell receptor (BCR) signalling molecules (n=5). Upregulation of T-cell costimulatory molecules after BCR and toll-like receptor (TLR)-7/TLR-8 stimulation was detected in cells from four subjects. To explore the role of these cells in SLE pathogenesis via T cell-dependent mechanisms, four subjects were analysed to detect the promotion of CD4+ T-cell activation and antibody-secreting cell (ASC) differentiation after CD4+ T-cell-B-cell cocultures. The aNAV B cells from four patients were used to assess cytokine secretion. RESULTS: The aNAV B cells of patients with SLE had increased expression of surface CD40, HLA-DR and interleukin-21 receptor (IL-21R) and FCRL5 molecules. With BCR stimulation, these cells greatly increased PLCγ2 phosphorylation. Integrated BCR and TLR-7/TLR-8 signals induced overexpression of CD40, CD86, IL-21R and HLA-DR on lupus aNAV B cells. In T-cell-B-cell cocultures, lupus aNAV B cells (with upregulated costimulatory molecules) promoted CD4+ T-cell proliferation and polarisation toward effector Th2 and Th17 cells. Importantly, in this coculture system, CD4+ T-cell signals enhanced aNAV B-cell differentiation into auto-ASCs and produced anti-DNA antibodies. The interaction between CD4+ T cell and aNAV B cell increased production of inflammatory cytokines (IL-6, IL-8 and IL-23). CONCLUSION: Cooperation between aNAV B cells and CD4+ T cells contributed to SLE pathogenesis by promoting both differentiation of pathogenic T cells (Th2 and Th17) and autoantibody secretion.

Predicting treatment response and clinicopathological findings in lupus nephritis with urine epidermal growth factor, monocyte chemoattractant protein-1 or their ratios.

INTRODUCTION: There is a need for sensitive and specific biomarkers to predict kidney damage and therapeutic response in lupus nephritis (LN). Monocyte chemoattractant protein-1 (MCP-1) and epidermal growth factor (EGF) are cytokines with divergent roles. EGF or EGF/MCP1 ratio have been shown to correlate with prognosis in primary glomerulonephritis, but there is limited information in lupus nephritis (LN). This study evaluated the roles of MCP-1, EGF or their ratio as biomarkers of histopathology and response to treatment in LN. METHODS: This was a cross-sectional and observational study. Baseline urine MCP-1 and EGF levels in systemic lupus erythematosus (SLE) patients and controls (total n = 101) were compared, and levels were correlated with clinicopathological findings and subsequent response to treatment. RESULTS: MCP-1 was higher in active LN (n = 69) compared to other SLE groups and controls, whereas EGF was not different. MCP-1 correlated with disease activity (proteinuria, renal SLEDAI, classes III/IV/V, and high activity index.) By contrast, EGF correlated with eGFR, but not with proteinuria, activity index, or class III/IV/V. MCP-1 was higher, and EGF was lower in high chronicity index. EGF/MCP-1 decreased with greater clinicopathological severity. In a subgroup with proliferative LN who completed six months of induction therapy (n = 41), EGF at baseline was lower in non-responders compared to responders, whereas MCP-1 was similar. By multivariable analysis, baseline EGF was independently associated with subsequent treatment response. Area under the curve for EGF to predict response was 0.80 (0.66-0.95). EGF ≥ 65.6 ng/ mgCr demonstrated 85% sensitivity and 71% specificity for response. EGF/MCP-1 did not improve the prediction for response compared to EGF alone. CONCLUSION: MCP-1 increased with disease activity, whereas EGF decreased with low GFR and chronic damage. Urine EGF may be a promising biomarker to predict therapeutic response in LN. EGF/MCP-1 did not improve the prediction of response.

Trichoscopic Signs in Dermatomyositis, Systemic Lupus Erythematosus, and Systemic Sclerosis: A Comparative Study of 150 Patients.

BACKGROUND: Hair and scalp involvement is prevalent in connective tissue diseases (CTDs). Trichoscopic features may provide a diagnostic implementation and enable differentiation among CTDs; however, a direct comparison of these signs among CTD patients is lacking. OBJECTIVES: To compare trichoscopic findings in dermatomyositis (DM), systemic lupus erythematosus (SLE), and systemic sclerosis (SSc) as well as determine their distinctive features and associations with disease activity. METHODS: Trichoscopic photographs were taken from DM, SLE, and SSc patients and further evaluated for hair shaft and scalp surface abnormalities. Data regarding patients' clinical manifestations, laboratory results, and disease activity were analyzed. RESULTS: One hundred fifty participants, consisting of 30 DM, 60 SLE, and 60 SSc patients, were included. Perifollicular red-brown pigmentation, brown scattered pigmentation, and white patches were exclusive findings in DM, SLE, and SSc, respectively (p < 0.001). A multinomial logistic regression analysis revealed that DM demonstrated higher odds for having microaneurysmal blood vessels than SLE and SSc (odds ratio [OR] = 22.22, 95% confidence interval [CI] = 1.73-285.13, p = 0.017, and OR = 15.34, 95% CI = 1.36-177.59, p = 0.029, respectively). Polymorphic vessels forming a telangiectatic network suggested SSc over SLE (OR = 12.83, 95% CI = 1.35-121.98, p = 0.026), while avascular areas were more pronounced in SSc than DM and SLE (OR = 43.24, 95% CI = 5.17-361.67, p = 0.001, and OR = 0.03, 95% CI = 0.01-0.24, p = 0.001, respectively). In a quantile regression analysis, perifollicular red-brown pigmentation, reduction in hair diameter, and the absence of thin arborizing vessels were linked to higher disease activity in DM, SLE, and SSc, respectively (all p < 0.05). CONCLUSIONS: Trichoscopy is a valuable tool possessing diagnostic and prognostic values for CTDs. Specific trichoscopic features allow adequate distinction between DM, SLE, and SSc and may help identify active disease.

Vaginal microbiota affects urinary tract infection risk in women with systemic lupus erythematosus: a pilot cross-sectional study from Thailand.

OBJECTIVE: The risk factors associated with urinary tract infections (UTIs) in patients with SLE remain uncertain. We evaluated the vaginal microbiota pattern and its potential UTI-associated risk factors. METHODS: A pilot cross-sectional study of patients with SLE was conducted at Ramathibodi Hospital, Bangkok, Thailand, during 2019-2020. Patients' demographic data and relevant information were collected. Vaginal microbiota was assessed in all patients and in 10 healthy volunteers. RESULTS: Fifty-two patients were enrolled (mean age: 46.1 years). All patients had SLE that was in low disease activity. As per the Simpson_e index, the within-group alpha diversity of the vaginal microbiota was low in the SLE with UTI and SLE receiving trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis groups. Multivariate logistic regression analysis revealed that TMP-SMX prophylaxis (adjusted OR (AOR), 30.96; 95% CI 3.63 to 264.11; p=0.002), elevated C3 levels (AOR, 35.33; 95% CI 1.33 to 936.67; p=0.033) and presence of Veillonella dispar in the vaginal microbiota (AOR, 6.68; 95% CI 1.27 to 35.07; p=0.025) were associated with UTI. CONCLUSIONS: The vaginal microbiota diversity differed between patients with lupus with and without UTI, and unnecessary administration of TMP-SMX prophylaxis may affect the alpha diversity of the vaginal microbiota.

Assessment of transition readiness in adolescents in Thailand with rheumatic diseases: a cross-sectional study.

BACKGROUND: Most childhood-onset rheumatic diseases are chronic health conditions, which need long-term care throughout adulthood. A well-organized transition care is challenging and patient assessment of transition skills is needed for transfer preparation to an adult care setting. The Transition Readiness Assessment Questionnaire (TRAQ) is used to assess transition skills in chronically ill patients. Currently, limited transition skill assessment data exist in pediatric patients with rheumatic diseases, especially in Asian countries. This study aimed to determine the transition readiness skills in patients with rheumatic diseases and ascertain predictive factors contributing to high transition readiness skills. METHODS: This is a cross-sectional study. All patients with rheumatic diseases aged 15-20 years were recruited. The TRAQ was cross-culturally adapted into the Thai language with good internal consistency and reliability. Patients completed the Thai TRAQ at the recent clinic visit and took the retest at a 2-week interval. Demographic data, baseline characteristics, clinical manifestations, and disease status were collected. Descriptive and logistic regression analyses were performed. RESULTS: A total of 111 patients with a mean age of 17.4 ± 1.8 years were included. Median (IQR) disease duration was 6.4 (3.2-9.0) years. The most common rheumatic disease was juvenile idiopathic arthritis (48.6%), followed by systemic lupus erythematosus (35.1%). The mean TRAQ score was 3.85 ± 0.69. Independent visits (OR 4.35, 95% CI 1.23-15.37) was a predictor of a high TRAQ score. Furthermore, dependent visits (OR 7.84, 95% CI 2.41-25.50) was a predictor of low TRAQ score in the "appointment keeping" domain, whereas inactive disease (OR 4.54, 95% CI 1.25-16.55) was a predictor of a low TRAQ score in "tracking health issues" domain. Lack of knowledge and skills on health insurance coverage, financial management, appointment arrangement, and coping with their illness were issues causing lower TRAQ score. CONCLUSIONS: Patients, who had independent visits, had a higher chance to obtain higher TRAQ scores, whereas patients, who had an inactive disease or dependent visits, had less transition readiness skills. Physicians and parents should prepare to transfer patients to adult care settings, mainly encouraging independent living skills.

The expansion of activated naive DNA autoreactive B cells and its association with disease activity in systemic lupus erythematosus patients.

BACKGROUND: Autoreactive B cells are well recognized as key participants in the pathogenesis of systemic lupus erythematosus (SLE). However, elucidating the particular subset of B cells in producing anti-dsDNA antibodies is limited due to their B cell heterogeneity. This study aimed to identify peripheral B cell subpopulations that display autoreactivity to DNA and contribute to lupus pathogenesis. METHODS: Flow cytometry was used to detect total B cell subsets (n = 20) and DNA autoreactive B cells (n = 15) in SLE patients' peripheral blood. Clinical disease activities were assessed in SLE patients using modified SLEDAI-2 K and used for correlation analyses with expanded B cell subsets and DNA autoreactive B cells. RESULTS: The increases of circulating double negative 2 (DN2) and activated naïve (aNAV) B cells were significantly observed in SLE patients. Expanded B cell subsets and DNA autoreactive B cells represented a high proportion of aNAV B cells with overexpression of CD69 and CD86. The frequencies of aNAV B cells in total B cell populations were significantly correlated with modified SLEDAI-2 K scores. Further analysis showed that expansion of aNAV DNA autoreactive B cells was more related to disease activity and serum anti-dsDNA antibody levels than to total aNAV B cells. CONCLUSION: Our study demonstrated an expansion of aNAV B cells in SLE patients. The association between the frequency of aNAV B cells and disease activity patients suggested that these expanded B cells may play a role in SLE pathogenesis.

Perception of contraceptive counseling and contraceptive use among systemic lupus erythematosus patients.

OBJECTIVES: (1) To evaluate the perception of contraceptive counseling and knowledge regarding the impact of unintended pregnancy and (2) examine the prevalence of, and predictors for contraceptive use among systemic lupus erythematosus (SLE) patients. STUDY DESIGN: A cross-sectional survey was conducted at the Rheumatology Clinic of a university hospital. SLE patients who attended the clinic from April 2018 to January 2019 and at risk for unintended pregnancy and were invited to be interviewed. The structured interview guide consisted of three parts: personal and obstetric information, perception of contraceptive counseling and knowledge about the impact of unintended pregnancy, and contraceptive use. RESULTS: The mean age of the 137 patients who gave informed consents was 34 ±â€¯8 years, with 47 patients (34%) stating that they had received contraceptive counseling. Seventy-five patients (52%) reported practicing contraception. The intention to not become pregnant (Odds Ratio; 95% CI = 7.28; 1.75-30.27), perception of adequate contraceptive counseling (2.77; 1.06-7.20) and discussion with partners and physicians about contraception (3.95; 1.64-9.50) were predictors for contraceptive use (p < 0.05). CONCLUSION: Most patients reported no contraceptive counseling with approximately half of the patients using contraceptive methods within the past three months. Desire to avoid pregnancy, perception of adequate contraceptive counseling, and the influence of partners and physicians were significant predictors for contraceptive use. IMPLICATIONS: Contraceptive counseling should be routinely included in discussions about disease processes and treatment plans, including access issues. Best practices for contraceptive counseling and integrated, multi-disciplinary team services should be developed and provided in clinical settings.

Efficacy and safety of rituximab biosimilar in refractory lupus.

AIMS: To characterise patients with refractory SLE receiving rituximab biosimilar (CT-P10) and to explore short-term efficacy and safety associated with rituximab biosimilar use. METHODS: We retrospectively analysed data from the medical records of patients with refractory SLE who received CT-P10 in Ramathibodi Hospital, Mahidol University, Thailand. Baseline characteristics, disease activity (modified Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)), response to treatment at 6 months after CT-P10 and infection over 6 months were recorded. RESULTS: Thirty-two patients with SLE received CT-P10 from April 2018 to June 2019. Of these, 29 (90.6%) were female and the mean±SD age was 36.8±15.2 years. The median (IQR) disease duration was 9.5 (1.3-13.0) years. All patients received glucocorticoid treatment and used 1.7±0.1 immunosuppressive agents at baseline, excluding antimalarial drugs. Baseline Systemic Lupus International Collaborating Clinics Damage Index score was 0.5 (0.0-1.0). Overall response, which was defined as a reduction in the modified SLEDAI score of ≥4, was achieved in 25.0% of patients at 6 months. The modified SLEDAI score reduced from 4 (1.3-8.0) at baseline to 1 (0.0-5.8) at 6 months (p=0.005). Response by active organ involvement was 71.8%. Serious infection occurred in four patients (12.5%), resulting in one death. The median time of onset of infection after CT-P10 infusion was 35.5 (17.0-72.5) days. CONCLUSION: Rituximab biosimilar is associated with improvement in active organ involvement in patients with refractory SLE. Infection occurred early after rituximab biosimilar infusion.

Cutaneous and Extracutaneous Manifestations of Behçet's Disease Linked to Its Disease Activity and Prognosis.

BACKGROUND: Behçet's disease is a potentially fatal vasculitis disorder involving vessels in both the arterial and venous systems. Cutaneous manifestation is the most common sign in Behçet's disease, but its relation to disease activity and prognosis is lacking. OBJECTIVE: Our study aims to determine the relationship between cutaneous, extracutaneous manifestations with Behçet's disease activity, morbidity, and mortality. MATERIALS AND METHODS: Patients diagnosed with Behçet's disease were identified by using the 1990 International Study Group for Behçet's disease criteria and/or the 2014 international criteria for Behçet's disease. Data regarding patients' clinical manifestations, laboratory results, disease activity, and prognosis were retrieved and analyzed. Disease activity was evaluated using the 2006 Behçet's disease current activity form (BDCAF). RESULTS: Of 119 patients, the mean age at diagnosis was 35.7 ± 10.7 years and 60% were female. Median disease duration was 96 months (IQR 48-168). Minor oral ulcer at the buccal mucosa was associated with lower median BDCAF score (p = 0.003), whereas minor oral ulcer at the tonsil was related to higher BDCAF score (p = 0.024). Male gender was associated with higher cumulative dose of corticosteroids (p = 0.003) and hospitalization (OR = 2.89 (95% CI [1.10, 7.57]), p = 0.031). Ocular manifestations were related to higher dose of corticosteroids (p = 0.002) and morbidity (OR = 4.39 (95% CI [1.57, 12.29]), p = 0.005). CONCLUSION: Our study suggests that different locations of minor oral ulcers help predict disease activity. Male gender and the presence of ocular manifestations resulted in less favorable outcomes for Behçet's disease.

Meta-analysis of genome-wide association study identifies FBN2 as a novel locus associated with systemic lupus erythematosus in Thai population.

BACKGROUND: Differences in the expression of variants across ethnic groups in the systemic lupus erythematosus (SLE) patients have been well documented. However, the genetic architecture in the Thai population has not been thoroughly examined. In this study, we carried out genome-wide association study (GWAS) in the Thai population. METHODS: Two GWAS cohorts were independently collected and genotyped: discovery dataset (487 SLE cases and 1606 healthy controls) and replication dataset (405 SLE cases and 1590 unrelated disease controls). Data were imputed to the density of the 1000 Genomes Project Phase 3. Association studies were performed based on different genetic models, and pathway enrichment analysis was further examined. In addition, the performance of disease risk estimation for individuals in Thai GWAS was assessed based on the polygenic risk score (PRS) model trained by other Asian populations. RESULTS: Previous findings on SLE susceptible alleles were well replicated in the two GWAS. The SNPs on HLA class II (rs9270970, A>G, OR = 1.82, p value = 3.61E-26), STAT4 (rs7582694, C>G, OR = 1.57, p value = 8.21E-16), GTF2I (rs73366469, A>G, OR = 1.73, p value = 2.42E-11), and FAM167A-BLK allele (rs13277113, A>G, OR = 0.68, p value = 1.58E-09) were significantly associated with SLE in Thai population. Meta-analysis of the two GWAS identified a novel locus at the FBN2 that was specifically associated with SLE in the Thai population (rs74989671, A>G, OR = 1.54, p value = 1.61E-08). Functional analysis showed that rs74989671 resided in a peak of H3K36me3 derived from CD14+ monocytes and H3K4me1 from T lymphocytes. In addition, we showed that the PRS model trained from the Chinese population could be applied in individuals of Thai ancestry, with the area under the receiver-operator curve (AUC) achieving 0.76 for this predictor. CONCLUSIONS: We demonstrated the genetic architecture of SLE in the Thai population and identified a novel locus associated with SLE. Also, our study suggested a potential use of the PRS model from the Chinese population to estimate the disease risk for individuals of Thai ancestry.

Clinical manifestations, clinical course, and outcomes of immunoglobulin G4-related disease.

BACKGROUND: Immunoglobulin G4-related disease (IgG4-RD) is an uncommon chronic systemic autoimmune disease, pathologically characterized by lymphoplasma cell and IgG4 plasma cell infiltration with storiform fibrosis. IgG4-RD is a new disease and is not yet widely recognized. The aim of this study was to describe the clinical manifestations and outcomes in Thai patients with IgG4-RD. METHODS: This multicenter retrospective cohort study included patients aged ≥ 18 years who were diagnosed with IgG4-RD, according to the 2011 comprehensive or consensus diagnostic criteria, between 2000 and 2019 in four academic centers in Thailand. Baseline characteristics, laboratory and pathologic findings, treatments, and outcomes were systematically reviewed. RESULTS: The study included 110 patients (71% male) with a mean age (SD) of 59.6 (13.3) years and median disease duration (interquartile range [IQR]) of 28.8 (14.6-53.5) months. Single organ involvement was observed in 60 patients (54.5%). Most patients (96%) had an IgG4 level of more than 135 mg/dL at presentation. Also, most (92%) were treated with corticosteroid (CS) alone or in combination with immunosuppressive agents. The most commonly used immunosuppressive agents were azathioprine (47%) and methotrexate (11%). Additionally, 20% required surgery, and 6.4% underwent stent insertion. One-quarter (26%), 37%, and 29% were in remission with successfully tapering CS, complete and partial response. Nevertheless, 22% relapsed, with a median time to relapse (IQR) of 22.2 (12.8-41.1) months. CONCLUSION: IgG4-RD is a chronic systemic autoimmune disease with diverse manifestations, response to treatment, and outcomes. Most patients responded well to treatments but with a notable relapse rate.

Prospective Pilot Study of Cyclophosphamide as an Adjunct Treatment in Patients With Adult-Onset Immunodeficiency Associated With Anti-interferon-γ Autoantibodies.

BACKGROUND: Adult-onset immunodeficiency associated with interferon-γ autoantibody (IGA) is an emerging disease. The majority of patients require both antimicrobial and immunosuppressive treatments. However, anti-CD20 therapy is not fully accessible in a resource-limited setting to date. BACKGROUND: The objectives of this work were to study the efficacy of cyclophosphamide treatment and the role of laboratory biomarkers for disease progression monitoring. METHODS: A prospective pilot cohort study was conducted among patients with anti-interferon-γ autoantibodies (IGA) who had recurrent infections and required long-term antimicrobial therapy between 2015 and 2018. The patients were categorized into 2 groups: receipt of intravenous cyclophosphamide (IVCY) and receipt of anti-CD20 therapy (RTX). Clinical and laboratory data were determined. RESULTS: A total of 17 IGA patients were enrolled. Prolonged fever was the most common manifestation, and the most common infection identified was nontuberculous mycobacterial infections. Both were found in 88.24% of all patients.After completion of IVCY, 9/11 patients achieved complete remission and tended to reach remission faster compared with individuals in the RTX group. The median duration from treatment initiation to remission (interquartile range) was 84 (42-154) days in the IVCY group and 99 (51-202) days in the RTX group. In remission patients, the biomarkers of interest had normalized after treatment, except interferon γ autoantibody titers. There were no differences in adverse events among the 2 groups. CONCLUSION: IVCY may be considered as alternative therapy in this population, especially in resource-limited countries. A comparable clinical outcome to RTX may support its use on a larger scale. However, further study is encouraged.

Performance of cytokine models in predicting SLE activity.

BACKGROUND: Identification of universal biomarkers to predict systemic lupus erythematosus (SLE) flares is challenging due to the heterogeneity of the disease. Several biomarkers have been reported. However, the data of validated biomarkers to use as a predictor for lupus flares show variation. This study aimed to identify the biomarkers that are sensitive and specific to predict lupus flares. METHODS: One hundred and twenty-four SLE patients enrolled in this study and were prospectively followed up. The evaluation of disease activity achieved by the SLE disease activity index (SLEDAI-2K) and clinical SLEDAI (modified SLEDAI). Patients with active SLE were categorized into renal or non-renal flares. Serum cytokines were measured by multiplex bead-based flow cytometry. The correlation and logistic regression analysis were performed. RESULTS: Levels of IFN-α, MCP-1, IL-6, IL-8, and IL-18 significantly increased in active SLE and correlated with clinical SLEDAI. Complement C3 showed a weakly negative relationship with IFN-α and IL-18. IL-18 showed the highest positive likelihood ratios for active SLE. Multiple logistic regression analysis showed that IL-6, IL-8, and IL-18 significantly increased odds ratio (OR) for active SLE at baseline while complement C3 and IL-18 increased OR for active SLE at 12 weeks. IL-18 and IL-6 yielded higher sensitivity and specificity than anti-dsDNA and C3 to predict active renal and active non-renal, respectively. CONCLUSION: The heterogeneity of SLE pathogenesis leads to different signaling mechanisms and mediates through several cytokines. The monitoring of cytokines increases the sensitivity and specificity to determine SLE disease activity. IL-18 predicts the risk of active renal SLE while IL-6 and IL-8 predict the risk of active non-renal. The sensitivity and specificity of these cytokines are higher than the anti-dsDNA or C3. We propose to use the serum level of IL-18, IL-6, and IL-8 to monitor SLE disease activity in clinical practice.