Efficacy and safety of tocilizumab in Chinese patients with systemic juvenile idiopathic arthritis: a multicentre phase IV trial.

OBJECTIVES: Given the limited tocilizumab (TCZ) treatment data for systemic juvenile idiopathic arthritis (sJIA) in China, we evaluated the long-term efficacy and safety of TCZ in Chinese patients with sJIA. METHOD: In this multicentre, interventional Phase IV study, patients with sJIA and inadequate clinical response to non-steroidal anti-inflammatory drugs/corticosteroids received TCZ infusions every 2 weeks based on body weight (< 30 kg, 12 mg/kg; ≥ 30 kg, 8 mg/kg), over a 52-week open-label period and an 8-week safety follow-up period. The primary endpoint was the proportion of patients with a JIA American College of Rheumatology (ACR) 30 response and absence of fever at Week 12. RESULTS: Sixty-two patients were enrolled and treated (12-mg/kg group, 34; 8-mg/kg group, 28). At Week 12, 87.1% (95% confidence interval 78.8%-95.4%) of patients had JIA ACR 30 response and absence of fever; Week 52 results were similar. The proportion of JIA ACR 30/50/70/90 responders rapidly increased at Week 12, up to Week 52. High-sensitivity C-reactive protein (hsCRP) levels decreased within 4 weeks; 44/58 patients (75.9%) with elevated baseline hsCRP recovered at Week 52. Childhood Health Assessment Questionnaire pain scores, disability index scores, and mean corticosteroid dose decreased over time. Height standard deviation score changes at Week 52 indicated catch-up growth. Most adverse events (AEs) were mild (serious AE incidence, 17.7%). No deaths or macrophage activation syndrome occurred. CONCLUSION: This is the first multicentre trial to report the efficacy and safety of TCZ in Chinese patients with sJIA at 52 weeks. No new safety concerns were found.

Trisomy 8 presentation by inflammatory manifestations and its response to thalidomide: two case reports and narrative review.

Objective: It has been recognized that there is a nexus among Trisomy 8 (T8), Behcet's disease (BD), and myelodysplastic syndrome (MDS). We reported a series of inflammatory features in 2 children with T8 without hematological involvement. Methods: 2 children with trisomy 8 who were excluded from MDS were retrospectively collected from the Department of Rheumatology and Immunology, Children's Hospital of Nanjing Medical University, Nanjing. Results: Patients developed a range of inflammatory manifestations before a diagnosis of T8. The clinical manifestations of T8 patients vary from normal to severely disabled. Glucocorticoids and thalidomide can effectively relieve inflammation in patients with T8. Conclusion: The early clinical manifestations of T8 in children lack specificity, and the diagnosis is mainly based on karyotype analysis, gastrointestinal endoscopy and bone marrow aspiration findings. Active and effective immunoregulatory therapy and long-term follow-up can improve the prognosis of patients with T8.

Single center clinical analysis of macrophage activation syndrome complicating juvenile rheumatic diseases.

BACKGROUND: Macrophage activation syndrome (MAS), an example of secondary hemophagocytic lymphohistiocytosis, is a potentially fatal complication of rheumatic diseases. We aimed to study the clinical and laboratory characteristics, treatment schemes, and outcomes of different rheumatic disorders associated with MAS in children. Early warning indicators of MAS have also been investigated to enable clinicians to make a prompt and accurate diagnosis. METHODS: Fifty-five patients with rheumatic diseases complicated by MAS were enrolled between January 2017 and December 2022. Clinical and laboratory data were collected before disease onset, at diagnosis, and after treatment with MAS, and data were compared between patients with systemic juvenile idiopathic arthritis (sJIA), Kawasaki disease (KD), and systemic lupus erythematosus (SLE). A random forest model was established to show the importance score of each variable with a significant difference. RESULTS: Most (81.8%) instances of MAS occurred during the initial diagnosis of the underlying disease. Compared to the active stage of sJIA, the platelet count, erythrocyte sedimentation rate, and fibrinogen level in sJIA-MAS were significantly decreased, whereas ferritin, ferritin/erythrocyte sedimentation rate, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and D-dimer levels were significantly increased. Ferritin level, ferritin/erythrocyte sedimentation rate, and platelet count had the greatest predictive value for sJIA-MAS. The level of IL-18 in the sJIA-MAS group was significantly higher than in the active sJIA group, whereas IL-6 levels were significantly lower. Most patients with MAS were treated with methylprednisolone pulse combined with cyclosporine, and no deaths occurred. CONCLUSIONS: Thrombocytopenia, ferritin levels, the ferritin/erythrocyte sedimentation rate, and elevated aspartate aminotransferase levels can predict the occurrence of MAS in patients with sJIA. Additionally, our analysis indicates that IL-18 plays an important role in the pathogenesis of MAS in sJIA-MAS.

Clinical and Genetic Spectrum of Nine Cases of NLRP3-Associated Autoinflammatory Disease (NLRP3-AID) and Identification of One Novel NLRP3 Mutation by Genetic Variation Analyses.

Purpose: NLRP3-associated autoinflammatory disease (NLRP3-AID) is characterized by gain-of-function variants in the NLRP3 gene. Since there are little literature focusing on pediatric NLRP3-AID in China, we aimed to elucidate the phenotypic and genotypic profiles of Chinese patients with NLRP3-AID. Methods: Patients with NLRP3-AID at three rheumatology centers in China were genotyped through whole exome sequencing or gene panel sequencing. Sanger sequencing was performed on all patients and their parents. Clinical phenotype, treatment, and prognosis were analyzed. Results: Nine patients with NLRP3-AID were enrolled between December 2014 and October 2022 with an average follow-up period exceeding 30 months. The median age of onset was 12 months, and 66.7% were younger than 3 years old. The diagnosis was significantly delayed and the median delay duration was 115 months. The patients most commonly presented with rash (100%), arthritis/arthralgia (88.9%), lymphadenopathy (88.9%), fever (77.8%), and growth retardation (44.4%). During acute attack, white blood cell, C-reactive protein, and/or erythrocyte sedimentation rate all increased in all cases, and inflammatory markers remained elevated beyond 7 days postfever resolution in 57.1% of patients (4/7). Two cases of chronic infantile neurological cutaneous articular syndrome (CINCA) had clubbed fingers, one with interstitial lung disease, a finding rarely reported. Treatment with glucocorticoids (77.8%) and biologic agents (33.3%) yielded 66% complete remission and 33% partial remission. Genetic analysis identified eight pathogenic NLRP3 missense mutations, including one novel mutation. Conclusions: Our study illuminated the distinct clinical and genetic features of Chinese NLRP3-AID patients, emphasizing the significance of early genetic screening. Despite delayed diagnosis, treatment primarily with glucocorticoids and biologic agents, led to favorable outcomes. Genetic heterogeneity, including a novel mutation, highlighted the complexity of NLRP3-AID in this population.

Efficacy and safety of canakinumab in systemic juvenile idiopathic arthritis, the first Chinese experience.

BACKGROUND: Systemic juvenile idiopathic arthritis (sJIA) is a severe form of juvenile arthritis that is characterized by chronic joint inflammation and systemic symptoms such as fever, rash, and organ involvement. Anti-IL-6 receptor monoclonal antibody tocilizumab is an effective treatment. However, some patients still experience persisting or recurrent symptoms and the real-world effectiveness of canakinumab in Chinese patients with sJIA has never been reported. Therefore, this study aimed to assess the efficacy and safety of canakinumab in Chinese patients with sJIA using real-world data. METHODS: We conducted a retrospective study on children with active sJIA. Clinical features, laboratory data, corticosteroid dosage, and adverse events (AEs) were collected at baseline and at 4, 8, 12, and 24 weeks after initiating canakinumab treatment. RESULTS: Seven female and four male patients were included in the study. All patients had previously been treated with tocilizumab and were administered canakinumab for 12.4 ± 3.4 months. Notably, significant improvements were observed in both clinical signs and symptoms as well as laboratory indicators. Four children under corticosteroid treatment were able to successfully discontinue their corticosteroid therapy: one at week 4, two at week 12, and one at week 24. Notably, there was a significant reduction in the number of tender and swollen joints (P = 0.0059) as well as the systemic juvenile arthritis disease activity score (P < 0.0001). The most common AE was infection, but no patients experienced serious AEs. No cases of macrophage activation syndrome or death were reported during the follow-up period. CONCLUSIONS: Canakinumab was found to be potentially efficacious and safe in Chinese patients with sJIA. No new AEs were observed with canakinumab treatment.

A retrospective study of infantile-onset Takayasu arteritis: experience from a tertiary referral center in China.

Objective: Takayasu artery (TAK) is a chronic inflammatory disease that mainly affects the aorta and its major branches and is rarely reported in infants. We aimed to summarize the clinical features of infant TA (I-TA) in a tertiary care center. Methods: We performed a retrospective study involving 10 infants diagnosed with TAK. A comprehensive evaluation of clinical, laboratory, radiographic features, disease activity, treatment and outcomes was carried out. Results: A consecutive cohort was composed of 8 girls and 2 boys, with an age at diagnosis of 11.1 (1.7-36) months. The median time to diagnosis and the average time to follow-up were 9.5 days (2-235 days) and 10.9 (1-21) months, respectively. The most common initial manifestations were malaise (80%), fever (70%), hypertension (50%) and rash (30%). The mean Pediatric Vasculitis Activity Score (PVAS), Takayasu Clinical Activity Score (ITAS-2010) and ITAS-A scores were 2.8/63, 2.6/51, and 5.6/54, respectively. All patients had aberrant laboratory parameters. The most common lesions were in the thoracic aorta (60%) and abdominal aorta (60%). Corticosteroids combined with cyclophosphamide followed by long-term mycophenolate mofetil were initiated in most cases (70%). Biologics were attempted in 5 cases. Mortality was 40%. Conclusions: It is challenging to diagnose TAK in infants in a timely manner. Considering the more vessels involved, more severe inflammation and higher mortality, aggressive treatment is warranted in infants. GCs and CYC treatment seem to be effective.

Long non-coding RNA ENSMUST00000197208 promotes a shift in the Th17/Treg ratio via the P2X7R-NLRP3 inflammasome axis in collagen-induced arthritis.

Recently, long non­coding RNAs (lncRNAs) have been implicated in several human diseases, including arthritis. However, the role of lncRNAs in regulating the Th17/Treg ratio during the progression of collagen-induced arthritis (CIA) is poorly understood. Therefore, the aim of this study was to determine the role of the lncRNA ENSMUST00000197208 and the P2X7R-NLRP3 inflammasome axis in changes in the Th17/Treg ratio in CIA. To achieve this, the distribution of T cell subgroups in the spleen cells of a CIA mouse model and control mice was examined. Additionally, we examined the expression profile of ENSMUST00000197208 in a CIA mouse model and healthy mice. The results showed that ENSMUST00000197208 expression was significantly upregulated in the CIA models compared with the control group. Additionally, the P2X7R-NLRP3 inflammasome axis participated in the pathogenesis of CIA and knockdown of ENSMUST00000197208 inhibited CD4+ T cell differentiation into Th17 cells. Compared with the control group, joint inflammation was less visible in NLRP3 knockout mice. Additionally, the P2X7R-NLRP3 inflammasome axis, which is downstream of ENSMUST00000197208, can be positively targeted and regulated by ENSMUST00000197208 through miR-107. Overall, the findings of this study showed that the "lncRNA ENSMUST00000197208-miR 107-P2X7R/NLRP3" axis plays an important role in CIA and knocking down ENSMUST00000197208 can efficiently inhibit Th17 differentiation by suppressing the P2X7R-NLRP3 inflammasome axis. Therefore, targeting this axis may represent a novel strategy for arthritis treatment.

tRF-21-LNK8KEP1B as a potential novel diagnostic biomarker for enthesitis-related arthritis.

OBJECTIVE: tRNA-derived fragments (tRFs) play crucial roles in the progression of various diseases, and widely distribute in human tissues, including blood and urine. The diagnosis of enthesitis-related arthritis (ERA) is based on the observation of clinical manifestations. Therefore, we aimed to investigate whether serum tRFs can be used as diagnostic markers for ERA. METHODS: Serum was collected from children admitted to the Children's Hospital Affiliated with Nanjing Medical University between February 2022 to October 2022. The expression profiles of tRFs in the serum of ERA patients (n = 5) and healthy controls (HCs; n = 5) were investigated using small RNA high-throughput sequencing. The level and diagnostic value of tRF-21-LNK8KEP1B were evaluated by real-time quantitative PCR in serum samples from 30 ERA patients and 31 HCs. The specificity and sensitivity of tRFs were determined using receiver operating characteristic analyses. Bioinformatics analysis was performed to explore and identify the potential biological pathways induced by tRFs. RESULTS: Ninety-eight upregulated and 63 downregulated tRFs were identified in the serum. We selected tRF-21-LNK8KEP1B as a candidate marker using KEGG pathway enrichment and PCR validation. tRF-21-LNK8KEP1B was substantially increased in the serum of ERA patients compared with that in HCs. The area under the curve (AUC) for tRF-21-LNK8KEP1B in the ERA group was 0.7849. CONCLUSIONS: Collectively, we demonstrated the promising role of serum tRF-21-LNK8KEP1B -levels as a diagnostic biomarker for ERA.

Novel Predictive Scoring System for Intravenous Immunoglobulin Resistance Helps Timely Intervention in Kawasaki Disease: The Chinese Experience.

Background: Approximately 10%-20% of patients with Kawasaki disease (KD) are nonresponsive to intravenous immunoglobulin (IVIG) treatment, placing them at higher risk of developing coronary heart lesions. Early detection of nonresponsiveness is crucial to curtail this risk; however, the applicability of existing predictive scoring systems is limited to the Japanese population. Our study aimed to identify a predictive scoring system for IVIG resistance in KD specific to the Chinese population. We aimed to assess the utility of three commonly used risk-scoring systems in predicting IVIG resistance and compare them to the newly developed predictive scoring system. Methods: A total of 895 patients with KD were enrolled in this retrospective review and divided into two groups: IVIG responders and nonresponders. Clinical and laboratory variables were compared between the two groups. Multivariable logistic regression models were used to construct a new scoring system. The utility of the existing and new scoring systems was assessed and compared using the area under the receiver operating characteristic curve. Results: Albumin levels, percentage of neutrophils, and hemoglobin were independent predictors of resistance by logistic regression analysis. The new predictive scoring system was derived with improved sensitivity (60.5%) and specificity (87.8%). The area under the receiver operating characteristic curve was 0.818. Conclusion: This study developed a novel risk-scoring system for predicting resistance to IVIG treatment in KD specific to the Chinese population. Although this new model requires further validation, it may be useful for improving prognostic outcomes and reducing the risk of complications associated with KD.

Evaluation of belimumab in treatment of Chinese childhood-onset systemic lupus erythematosus: a prospective analysis from multicenter study.

OBJECTIVE: The aim of this study is to identify whether low lupus disease activity status (LLDAS) and clinical remission (CR) of belimumab plus standard of care (SoC) therapy are achievable goals in childhood-onset SLE (cSLE). METHODS: This multicentre, one arm pre-post intervention study was conducted at 15 centers in China. The primary end point was to describe the proportion of patients who achieved LLDAS and CR after 3, 6, and 12 months after treatment with belimumab plus SoC therapy. A multiple regression model was used to impute missing data. A Poisson regression model was used to calculate the effect of belimumab treatment on the reduced risk of serious diseases and the incidence of new damage. RESULT: 193 (92.2% female) with active cSLE from 15 centers were included. At 3, 6 and 12 months, the proportion of LLDAS (CR) was 12.4% (1.0%), 25.6% (4.5%) and 70.3% (29.7%), respectively. The mean SELENA-SLEDAI score decreased from 11.0 at baseline to 3.7, 2.9 and 1.7 at 3, 6, and 12 months. At baseline, all patients received steroids at a mean (SD) prednisone equivalent dose of 31.0 (18.2) mg/day, which decreased to 19.4 (10.8) mg/day at month 3, 12.6 (7.2) mg/day at month 6 and 6.7 (5.3) mg/day at month 12. The symptoms and immunological indicators were also significantly improved. CONCLUSION: This is the first and largest sample size prospective clinical intervention study of cSLE patients treated with belimumab in China. LLDAS and CR were attainable treat-to-target of belimumab plus SoC therapy in cSLE.

Effectiveness of tumor necrosis factor inhibitors in children with enthesitis-related arthritis: a single-center retrospective analysis.

Objective: In children with enthesitis-related arthritis (ERA), the hip and sacroiliac joint function might be impaired if not properly treated. We sought to evaluate the effectiveness of anti-tumor necrosis factor-α (TNF-α) therapy using the inflammatory indicators, Juvenile Arthritis Disease Activity Score 27 (JADAS27) and magnetic resonance imaging (MRI). Methods: We conducted a single-center retrospective study of 134 patients with ERA. We evaluated the effect of anti-TNF therapy on the inflammatory indicators, active joint count, MRI quantitative score, and JADAS27 over 18 months. We used the Spondyloarthritis Research Consortium of Canada (SPARCC) and the Hip Inflammation MRI Scoring System (HIMRISS) scoring systems for hip and sacroiliac joints scoring. Results: The average age of onset of children with ERA was 11.62 ± 1.95 years, and they were treated with disease-modifying antirheumatic drugs (DMARDs) combined with biologics (n = 87, 64.93%). There were no differences in HLA-B27 positivity between the biologics and non-biologics treatment groups [66 (49.25%) vs. 68 (50.75%), P > 0.05]. Children who received anti-TNF (71 received etanercept, 13 adalimumab, 2 golimumab, and 1 infliximab) therapy improved significantly. Children with ERA used DMARDs and biologics at baseline (Group A) were followed up to 18 months, and their active joint count (4.29 ± 1.99 vs. 0.76 ± 1.33, P = 0.000), JADAS27 (13.70 ± 4.80 vs. 4.53 ± 4.52, P = 0.000) and MRI quantitative scores (P = 0.001) were significantly lower than those at baseline. Some of the patients (n = 13, 9.70%) were treated with DMARDs at the onset of the disease, but did not show significant improvement (Group B). After 6-18 months of switching to anti-TNF therapy, related indicators of the children were significantly lower than at baseline and 1 month (P < 0.013). At 18 months, a total of 33 patients (n = 74, 44.59%) in Group A and 7 (n = 13, 53.85%) in Group B reached inactive state. Conclusion: Eighteen months after diagnosis, anti-TNF therapy was found to be effective in children diagnosed with ERA. MRI is important for the early diagnosis of juvenile idiopathic arthritis. TNF-α inhibitors can significantly improve the clinical manifestations of sacroiliac joint and hip involvement in patients with ERA. Overall, the real-world study provides more evidence for precision diagnosis and treatment for other hospitals, families and patients.

Pathogenic Gene Spectrum and Clinical Implication in Chinese Patients with Lupus Nephritis.

BACKGROUND: Lupus nephritis is a rare immunological disorder. Genetic factors are considered important in its causation. We aim to systematically investigate the rare pathogenic gene variants in patients with lupus nephritis. METHODS: Whole-exome sequencing was used to screen pathogenic gene variants in 1886 probands with lupus nephritis. Variants were interpreted on the basis of known pathogenic variants or the American College of Medical Genetics and Genomics guidelines and studied by functional analysis, including RNA sequencing, quantitative PCR, cytometric bead array, and Western blotting. RESULTS: Mendelian form of lupus nephritis was confirmed in 71 probands, involving 63 variants in 39 pathogenic genes. The detection yield was 4%. The pathogenic genes enriched in nuclear factor kappa-B (NF-κB), type I interferon, phosphatidylinositol-3-kinase/serine/threonine kinase Akt (PI3K/AKT), Ras GTPase/mitogen-activated protein kinase (RAS/MAPK), and Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathways. Clinical manifestation patterns were diverse among different signaling pathways. More than 50% of the pathogenic gene variants were reported to be associated with lupus or lupus nephritis for the first time. The identified pathogenic gene variants of lupus nephritis overlapped with those of autoinflammatory and immunodeficiency diseases. Inflammatory signatures, such as cytokine levels of IL-6, IL-8, IL-1 ß , IFN α , IFN γ , and IP10 in serum and transcriptional levels of interferon-stimulated genes in blood, were significantly higher in patients with pathogenic gene variants compared with controls. The overall survival rate of patients with pathogenic gene variants was lower than those without pathogenic gene variants. CONCLUSIONS: A small fraction of patients with lupus nephritis had identifiable pathogenic gene variants, primarily in NF-κB, type I interferon, PI3K/AKT, JAK/STAT, RAS/MAPK, and complement pathways.

Axial involvement in enthesitis-related arthritis: results from a single-center cohort.

BACKGROUND: Axial involvement in children with enthesitis-related arthritis (ERA) has characteristics that differ from those of peripheral involvement. This study characterized their clinical characteristics and treatment. METHODS: Patients with ERA at the Children's Hospital of Nanjing Medical University between January 2018 and December 2020 were included. The ERA cohort was divided into two based on the presence or absence of axial joint involvement. Demographic characteristics, clinical features, and treatments were described and compared. RESULTS: In total, 105 children with ERA were enrolled (axial ERA, n = 57; peripheral ERA, n = 48). The age at disease onset of the axial group tended to be higher (11.93 ± 1.72 vs. 11.09 ± 1.91 years) and the diagnosis delay was bigger in patients with axial ERA (10.26 ± 11.66 months vs. 5.13 ± 7.92 months). The inflammatory marker levels were significantly higher in patients with axial. There were no differences in HLA-B27 positivity between the groups (34 [59.65%] vs. 28 [58.33%], P > 0.05). Hip involvement was more frequent in the axial group (52.63% vs 27.08%; X2 = 7.033). A total of 38 (66.67%) and 10 (20.83%) patients with axial and peripheral ERA, respectively, were treated with biological disease-modifying anti-rheumatic drugs (DMARDs) at diagnosis. The administration of biologics increased gradually in the axial ERA group, peaking at 18 months and decreasing thereafter, whereas that in the peripheral ERA group peaked at 6 months and began to decline thereafter. CONCLUSIONS: Axial ERA is a persistent active disease and requires a more aggressive treatment. Classification and early recognition of axial involvement may help with timely diagnosis and appropriate management.

Purine metabolites promote ectopic new bone formation in ankylosing spondylitis.

Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease that mainly affects the axial skeleton, whose typical features are inflammatory back pain, bone structural damage and pathological new bone formation. The pathology of ectopic new bone formation is still little known. In this study, we found increased purine metabolites in plasma of patients with AS. Similarly, metabolome analysis indicated increased purine metabolites in both serum of CD4-Cre; Ptpn11fl/fl and SHP2-deficient chondrocytes. SHP2-deficient chondrocytes promoted the growth of wild type chondrocytes and differentiation of osteoblasts in CD4-Cre; Ptpn11fl/fl mice, which spontaneously developed AS-like bone disease. Purine metabolites, along with PTHrP derived from SHP2-deficient chondrocytes, accelerated the growth of chondrocytes and ectopic new bone formation through PKA/CREB signaling. Moreover, Suramin, a purinergic receptor antagonist, suppressed pathological new bone formation in AS-like bone disease. Overall, these results highlight the potential role of targeting purinergic signaling in retarding ectopic new bone formation in AS.

Inositol-Triphosphate 3-Kinase C and DNA Methylation Involvement in NLRP3 Inflammasome Activation in Kawasaki Disease.

OBJECTIVE: To evaluate ITPKC and NLRP3 expression in children with Kawasaki disease (KD) and investigate the relationship between serum pro-inflammatory cytokines triggered by NLRP3 and inflammatory indices. Simultaneously, the methylation level in the ITPKC promoter was evaluated in children with KD. METHODS: Children who satisfied the American Heart Association diagnostic criteria for KD were enrolled in the study from August 2018 to January 2019. The levels of ITPKC, NLRP3, IL-1ß, and IL-18 were measured. The effect of DNA methylation on the activity of the ITPKC promoter was observed. Methylation-specific PCR was used to verify methylation modification of the ITPKC promoter region in children with KD. RESULTS: ITPKC expression was downregulated in patients with KD, whereas NLRP3 was upregulated. Expression of the downstream cytokine, IL-18, was significantly upregulated in children with KD and correlated positively with inflammatory indices. Modifying DNA methylation significantly decreased the luciferase activity of the plasmid containing the ITPKC promoter region and thus, may inhibit ITPKC gene promoter activity. Furthermore, methylation modification was observed in the ITPKC promoter region of children with KD. CONCLUSION: Modification of DNA methylation inhibits ITPKC promoter activity and is involved in NLRP3 inflammasome activation in children with KD.

Case report: A STAT1 gain-of-function mutation causes a syndrome of combined immunodeficiency, autoimmunity and pure red cell aplasia.

Inherited autosomal dominant gain-of-function (GOF) mutations of signal transducer and activator of transcription 1 (STAT1) cause a wide range of symptoms affecting multiple systems, including chronic mucocutaneous candidiasis (CMC), infections, and autoimmune disorders. We describe a rare case of STAT1 mutation with recurrent CMC, lung infections, and anemia. According to the whole-exome sequencing (WES), the patient was genetically mutated in STAT1 GOF (c.854A>G, p.Q285R), and bone marrow biopsy suggested pure red cell aplasia (PRCA). As a functional verification, STAT1 levels and phosphorylation (p-STAT1) of peripheral blood mononuclear cells (PBMCs) following IFN-γ stimulation in STAT1 GOF patient was higher than in the healthy control. Combination therapy of blood transfusion, antimicrobials, intravenous immunoglobulin, methylprednisolone, and the Janus Kinase (JAK) specific inhibitor ruxolitinib was used during treatment of patients. The patient also received a hematopoietic stem cell transplant (HSCT) to help with infections and anemia. This is the first reported case of STAT1 GOF disease complicated with PRCA. This complication might be attributed to immune disorders caused by STAT1 GOF. Furthermore, ruxolitinib may be a viable therapeutic option before HSCT to improve disease management.