Primary immunodeficiency diseases (PIDs) patients may show systemic lupus erythematosus (SLE)-like autoimmunity disorders, such as cytopenias, as well as polyarthritis, which leads to concerns of misdiagnosis. We diagnosed three RALD cases between 2015 and 2018, who were suspected as SLE and summarized clinical characteristics. We collected and analyzed the clinical data of the 3 cases. DNA was extracted from the patients’ and their parents’ peripheral blood as well as oral mucosa cells, hair follicles, and nails. Genes were detected with the application of gene trapping high-throughput sequencing using PIDs panel and suspicious gene or mutation was further verified by Sanger sequencing. 1. Clinical features: On the one hand, the patients presented with severe thrombocytopenia, facial erythema, arthritis, positive autoantibodies and other manifestations, supporting the diagnosis of SLE. On the other hand, symptoms including early onset ages, recurrent infections, lymphadenopathy, hepatosplenomegaly, monocytosis and hypergammaglobulinemia, were common observed in PIDs. 2. Gene analysis: NRAS mutations (c.38G > A, p.G13D or c.37G > T, p.G13C) were found in the blood of the patients. Besides, the same set of mutations was detected in buccal mucosa of patient 1 and nails of patient 3 while the frequency was much lower. However, no mutation was found in other tissues or in their parents’ blood. Consequently, they were NRAS somatic mutated RALD. For those early-onset SLE-like patients with predominant hematologic disorders, monocytosis, recurrent infectious history, accompanied with hepatosplenomegaly and lymphadenopathy, a genetic screening of PIDs might be required.

Background: NLRP3-associated autoinflammatory disease (NLRP3-AID), caused by mutations of NLRP3, is one of the autoinflammatory diseases affecting inflammasomes. Since there are little cases of Chinese NLRP3-AID, we reported 14 Chinese NLRP3-AID patients in our center and summarized the clinical features of all Chinese patients by reviewing the literature. Results: Fourteen patients had been diagnosed as NLRP3-AID in our center. 12 different NLRP3 variants were identified, among which one is novel: p.Leu361Trp. Rash, recurrent fever, arthritis/arthralgia, uveitis, sensorineural deafness, symptoms of central neural systems (CNS), and increased inflammatory markers (including CRP, ESR, except Ferritin) were the common findings in Chinese patients. The frequencies of fever, neurological symptoms, musculoskeletal manifestations and ocular manifestations in Chinese patients might differ from that of patients from other regions. Besides, we also found clubbing fingers and optic neuritis in some NLRP3-AID patients, which were not commonly mentioned in previous reports. Conclusion: In our study, we expanded the clinical spectrum as well as the genetic pathogenic variants of NLRP3-AID. We also found that there were some differences between Chinese patients and patients from other regions, and that Chinese patients were more likely to develop severe symptoms.

Background: Monogenic autoinflammatory diseases (AIDs) are rare inflammatory diseases caused by genetic variants. The pathogenesis is complex and treatment options are limited. This study aimed to describe the safety and efficacy of thalidomide in the treatment of monogenic AIDs. Methods: This was a single-center, single-arm, real-world study. From September 2016 to August 2021, patients with monogenic AIDs who met the inclusion and exclusion criteria were given thalidomide for 12 months. There was a 3-month run-in period before dosing. The efficacy and adverse events were evaluated and recorded every 3 months. After 3 and 12 months of thalidomide treatment, clinical manifestations, disease activity score, inflammatory markers, and background medication adjustments were compared with baseline for efficacy analyses. Results: A total of 16 patients entered this study, including 3 with Aicardi-Goutières syndrome (AGS), 4 Blau syndrome, 2 chronic infantile neurologic cutaneous articular syndrome (CINCA), 2 A20 haploinsufficiency (HA20), 1 adenosine deaminase 2 deficiency(DADA2), 1 familial Mediterranean fever (FMF),1 tumor necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS), 1 PLCγ2-associated antibody deficiency and immune dysregulation (PLAID), and 1 stimulator of interferon genes-associated vasculopathy with onset in infancy(SAVI). The efficacy rate in the 16 patients after 3-month and 12-month thalidomide treatment in patients was 56.3%. Twelve patients completed the study, the fever improved in all of them, rash improved in 7 patients, and 5 patients stopped using glucocorticoids or other immunosuppressive agents. C-reactive protein was normal in 8 patients and erythrocyte sedimentation rate was normal in 11 patients. Anorexia and nausea occurred in 2 cases, with no other reported drug-related adverse reactions. Conclusion: The largest cohort of monogenic AIDs with the treatment of thalidomide demonstrated that thalidomide can help reduce disease activity and inflammation, reduce the dosage of glucocorticoids, and improve clinical outcomes. Thalidomide is relatively safe in monogenic AIDs.

Objective: Childhood‐onset lupus nephritis (LN) tends to be more severe than in adults. A significant correlation between remission at 3 months of induction therapy and remission after 3 years was found in adults. While few studies on the risk factors of poor early prognosis in children with LN were made. Thus, this study investigated the risk factors of early poor response to help doctors develop effective treatment strategies.Methods: A total of 99 LN children at Peking Union Medical College Hospital from January 2012 to January 2018 were evaluated and clinical data were retrospectively collected. In the study, a complete remission (CR) was defined as laboratory test results were completely normal, including blood routine, renal function, albumin, complement, and erythrocyte sedimentation rate, and the 24‐h urinary total protein (24 h UTP) was less than 150 mg. After 3 months of treatment, 15 children achieved CR, and they were in good prognosis group (n = 15). While 84 did not achieve CR, and they were in poor prognosis group (n = 84). We compared the differences of clinical and laboratory indicators between the two groups.Results: According to inclusion and exclusion criteria, 99 of 116 children with LN were included in this study. And 15 LN children were in good prognosis group. While 84 patients were in poor prognosis group. The incidence of rash (32.1% vs. 6.7%, p = 0.036) and oral ulcer (81.0% vs. 53.3%, p = 0.027) in poor prognosis group is higher than that in the good prognosis group. The 24 h UTP (g) [2.46 (1.41, 4.86) vs. 0.56 (0.30, 0.66), p < 0.001] and the serum creatinine (umol/L) [53.0 (40.3, 65.0) vs. 39.0 (29.8, 51.5), p = 0.017] were higher in poor prognosis group. The albumin (g/L) (28.7 ± 8.1 vs. 34.5 ± 5.3, p = 0.003) is lower in poor prognosis group. Logistic regression analysis showed that rash (p = 0.036), oral ulcer (p = 0.027), high 24 h UTP (p < 0.001), high creatinine (p = 0.017), and low serum albumin (p = 0.003) were significantly associated with poor early prognosis in childhood‐onset LN.Conclusion: The occurrence of rash cannot be ignored, especially for children with oral ulcers, a comprehensive evaluation of each system should be carried out, so as not to cause inactive treatment and affect the prognosis. High 24 h UTP have a positive predictive value for the early poor outcome of childhood‐onset LN. Active control of proteinuria and achieving rapid renal remission is crucial for good prognosis.

Gain-of-function variants in stimulator of interferon genes (STING1) are known to cause STING-associated vasculopathy with onset in infancy (SAVI), a disorder characterized by cutaneous vasculopathy, interstitial lung disease (ILD), and systemic inflammation. Here, we report a novel STING1 N188H variant in a patient who met the classification criteria for systemic lupus erythematosus (SLE) but lacked typical SAVI features. In vitro assays demonstrated that the N188H variant drives constitutive STING activation and enhances type I interferon signaling. Consistent with this, the patient exhibited elevated interferon-stimulated genes (ISGs) expression, and RNA sequencing confirmed significant upregulation of type I IFN signaling compared to healthy controls. Our findings expand the molecular spectrum of STING-associated disease.