Background: Haploinsufficiency of A20 (HA20) is an immune dysregulation disorder caused by loss-of-function TNFAIP3 mutations. This international multicenter study aimed to delineate its clinical spectrum, genetic basis, and natural history. Methods: A cross-sectional, retrospective analysis was conducted in HA20 patients with pathogenic or likely pathogenic TNFAIP3 variants. Clinical, laboratory and treatment data were assessed. Clustering analysis was applied to evaluate clinical features and disease phenotypes. Patients were stratified by age (< 16 years vs ≥ 16 years), country of origin (China vs U.S.), and gender. Results: A total of 185 patients from 41 clinics across 7 countries were included (median onset 3.3 years). Common clinical features were mucocutaneous involvement (80.5%), recurrent fever (63.3%), gastrointestinal symptoms (58.6%), cytopenias (56.6%), arthritis/arthralgia (46.7%), and recurrent infections (35.5%). Compared with adults and patients from the U.S. cohort, intestinal ulcers were significantly more frequent in children and patients from the Chinese cohort (P = 0.002 and P < 0.0001, respectively), whereas uveitis was less common in these groups (P = 0.001 and P < 0.0001, respectively). Hierarchical clustering of clinical disease phenotypes based on Pearson distance identified two major clusters, an autoinflammation-predominant phenotype and an autoimmune-predominant phenotype. The autoinflammation-predominant phenotype was more common in children and patients from the Chinese cohort (P = 0.033 and P = 0.003, respectively). A total of 89 pathogenic TNFAIP3 mutations were identified, including 46 novel variants. Large deletions were associated with neurologic disease and developmental delay (P = 0.0054 and P = 0.0245, respectively); however, there were no clear association between disruptions of specific functional A20 domains and onset age or phenotype. Therapeutically, TNF and IL-1 inhibitors were effective in most patients, with thalidomide and JAK inhibitors used in refractory cases; 51.5% had achieved minimal disease activity at the most recent follow-up. Conclusions: HA20 is a common dominantly inherited immune dysregulation disorder with phenotypic heterogeneity and potential age-dependent evolution. This large international cohort highlights diagnostic and therapeutic strategies to advance evaluation and management of HA20. ### Competing Interest Statement WG and GY are employees of Chigene (Beijing) Translational Medical Research Center Co. Ltd and Beijing Quanpu Medical Laboratory Co., Ltd. DMS receives consulting fees from Sobi and grant support from Sobi and Eli Lilly. The others declare no competing interest. ### Funding Statement T.H. received grant 82302056 from the National Natural Science Foundation of China. Q.Z. received grants 82225022, 32141004 and 32321002 from the National Natural Science Foundation of China and 2024YFC2511002 from the National Key Research and Development Program of China. J.Y. received grant SZSM202411012 supported by Sanming Project of Medicine in Shenzhen. D.M.S. received grants by Jeffrey Modell Foundation, Eli Lilly, Sobi, Samuel and Emma Winters Foundation. J.W received grants 82394420, 82394423, 82402121 from the National Natural Science Foundation of China and grant 2023M733104 from China Postdoctoral Science Foundation. S.W. received grant 82402118 from the National Natural Science Foundation of China. L.G. received the grant LHDMY23H100005 from Joint Funds of the Zhejiang Provincial Natural Science Foundation of China. X.Y. received the grants 82394420, 82394424 and 82471844 from the National Natural Science Foundation of China, the Hundred-Talent Program of Zhejiang University, grant 2021R01012 from Leading Innovative and Entrepreneur Team Introduction Program of Zhejiang and Key Technology Breakthrough Program of Ningbo Sci-Tech Innovation YONGJIANG 2035 (Grant No. 2024Z221). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics committee/IRB of Shenzhen Children's Hospital and University of Pittsburgh gave ethical approval for this work I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study and not in the manuscript are available upon reasonable request to the authors

VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is an adult-onset, X-linked clonal autoinflammatory disease caused by somatic mutations in the UBA1 gene, characterized by systemic inflammation accompanied by hematologic clonal abnormalities. Somatic UBA1 mutations result in impaired ubiquitination, disruption of protein homeostasis, and sustained activation of inflammatory signaling pathways, including nuclear factor-κB and Janus kinase-signal transducer and activator of transcription (JAK-STAT), which together constitute the core pathogenic mechanism. The disease involves multiple systems and tissues including the hematologic system, skin, cartilage and respiratory system, showing remarkable clinical heterogeneity. Diagnosis depends primarily on the combination of characteristic clinical manifestations and molecular confirmation of UBA1 mutations. Current therapeutic strategies lack a unified standard: glucocorticoids can rapidly control inflammation but are associated with high relapse rates, whereas targeted therapies such as JAK inhibitors, interleukin inhibitors, and hypomethylating agents show variable efficacy, and allogeneic hematopoietic stem cell transplantation offers curative potential in patients with concomitant myelodysplastic syndrome. This review systematically summarizes the genetic background, molecular mechanisms, clinical spectrum, diagnostic criteria, and therapeutic advances of VEXAS syndrome.

Porphyria cutanea tarda (PCT) is a hepatic porphyria often triggered by hepatitis C virus (HCV) infection, iron overload, or environmental exposure. Congenital dyserythropoietic anemia type II (CDA II) caused by SEC23B mutations leads to ineffective erythropoiesis and secondary iron accumulation. We report a 34-year-old man with genetically confirmed SEC23B-mutated CDA II who developed photosensitive bullae associated with chronic HCV genotype 1b infection, hyperbilirubinemia, and severe iron overload. Urinary porphyrins were positive, and skin biopsy showed subepidermal bullae with PAS-positive deposits, supporting the diagnosis of PCT. After unsuccessful therapy with hydroxychloroquine, treatment with sofosbuvir/velpatasvir achieved sustained virologic response, resolution of skin lesions, and marked ferritin reduction. This case illustrates that viral and metabolic stressors can trigger PCT in CDA II patients with possible hepatic involvement, underscoring the importance of recognizing combined genetic and infectious factors in rare hematologic disorders.

Monoclonal gammopathy of clinical significance (MGCS) refers to disorders in which small B-cell or plasma-cell clones produce pathogenic monoclonal immunoglobulins that cause organ injury independent of tumor burden. Because the clinical spectrum is heterogeneous and diagnostic criteria remain evolving, MGCS is frequently underrecognized, particularly when organ manifestations precede detectable paraproteinemia. We report a 52-year-old man with multisystem manifestations including cutaneous xanthomatosis, inflammatory myopathy, cryoglobulinemia, and possible cardiac involvement. The patient initially presented with progressive polymyalgia, leukopenia, and yellow-brown cutaneous plaques. Immune abnormalities had been documented several years before detection of monoclonal protein. Laboratory evaluation revealed IgG-λ monoclonal gammopathy with type I cryoglobulinemia, complement consumption, and autoantibody positivity, indicating systemic immune activation. Bone marrow examination demonstrated only 1.4% λ-restricted clonal plasma cells. Skin biopsy confirmed xanthomatous infiltration, while muscle biopsy showed myopathic changes without amyloid deposition. Cardiac imaging demonstrated asymmetric septal hypertrophy with patchy late gadolinium enhancement. Treatment with bortezomib–cyclophosphamide–dexamethasone led to marked clinical improvement, including resolution of myalgia, regression of skin lesions, normalization of leukopenia, and disappearance of cryoglobulins, although low-level paraprotein persisted. This case highlights that immune-mediated organ injury may precede measurable clonal expansion in MGCS and supports the concept that pathogenic monoclonal immunoglobulins can act as immune effectors driving systemic inflammation.

Pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome is a rare autosomal dominant hereditary autoinflammatory disease caused by PSTPIP1 gene variants and belongs to the PSTPIP1-associated inflammatory diseases (PAIDs). Its core clinical manifestations include recurrent pyogenic arthritis, pyoderma gangrenosum, and severe acne with onset in childhood or adolescence. Some patients may also present with multisystem involvement, such as inflammatory bowel disease and scleritis. Inflammation markers, such as CRP and ESR, are often significantly elevated. Treatment mainly involves targeted inhibition of inflammatory pathways, such as IL-1 inhibitors and TNF-α inhibitors. In this article, we report a Chinese patient with PAPA syndrome with disease onset at 13 years of age, whose main manifestations were pyoderma gangrenosum and acne. Genetic testing revealed a de novo PSTPIP1 gene variant (c.748G>A, p.Glu250Lys). We also reviewed recent literature on PAPA syndrome, summarizing its clinical manifestations, diagnosis, and treatment to enhance physicians’ understanding of the condition.

Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) is an intracellular innate immune sensor. Its functions have been extensively studied. Variants in the NOD2 gene are associated with several human diseases. This report provides a comprehensive review of these diseases and biomedical and immunological roles of NOD2. Blau syndrome is an autosomal dominant disease primarily occurring in children and is caused by highly penetrant NOD2 variants. Approximately 40

BACKGROUND:Haploinsufficiency of A20 (HA20) is an immune dysregulation disorder caused by loss-of-function TNFAIP3 mutations. This international multicenter study aimed to delineate its clinical spectrum, genetic basis, and natural history. METHODS:A cross-sectional retrospective analysis was conducted in HA20 patients with pathogenic or likely pathogenic TNFAIP3 variants. Clinical, laboratory, and treatment data were assessed. Clustering analysis was applied to evaluate clinical features and disease phenotypes. Patients were stratified by age (<16 years vs ≥16 years), country of origin (China vs United States), and sex. RESULTS:A total of 185 patients from 41 clinics across 7 countries were included (median age at onset, 3.3 years). Common clinical features were mucocutaneous involvement (80.5%), recurrent fever (63.3%), gastrointestinal symptoms (58.6%), cytopenia (56.6%), arthritis/arthralgia (46.7%), and recurrent infections (35.5%). Compared with adults and patients from the US cohort, intestinal ulcers were significantly more frequent in children and patients from the Chinese cohort (P = .002 and P < .0001, respectively), whereas uveitis was less common in these groups (P = .001 and P < .0001, respectively). Hierarchical clustering of clinical disease phenotypes based on Pearson distance identified two major clusters, an autoinflammation-predominant phenotype and an autoimmune-predominant phenotype. The autoinflammation-predominant phenotype was more common in children and patients from the Chinese cohort (P = .033 and .003, respectively). A total of 89 pathogenic TNFAIP3 mutations were identified, including 46 novel variants. Large deletions were associated with neurologic disease and developmental delay (P = .0054 and .0245, respectively); however, there were no clear associations between disruptions of specific functional A20 domains and age at onset or phenotype. Therapeutically, TNF and IL-1 inhibitors were effective in most patients, with thalidomide and JAK inhibitors provided in refractory cases; 51.5% had obtained minimal disease activity at most recent follow-up. CONCLUSIONS:HA20 is a common dominantly inherited immune dysregulation disorder with phenotypic heterogeneity and potential age-dependent evolution. This large international cohort highlights diagnostic and therapeutic strategies to advance evaluation and management of HA20.

Blau syndrome (BS) is a rare autoinflammatory disorder characterized by the clinical triad of uveitis, dermatitis, and arthritis. While the clinical spectrum is well-documented, data on the longitudinal efficacy and durability of tumor necrosis factor-α (TNF-α) inhibitors remain limited. This study aimed to evaluate the longitudinal treatment trajectories, safety, and long-term outcomes of TNF-α inhibitors in a Chinese cohort. This longitudinal observational cohort study analyzed clinical data from 13 Chinese patients diagnosed with BS at Peking Union Medical College Hospital between 2015 and 2025. Whole-exome sequencing was performed in all cases. The cohort was comprehensively evaluated in terms of demographic characteristics, clinical manifestations, genetic findings, genotype-phenotype correlations, and treatment outcomes (specifically focusing on the long-term durability and treatment switching of TNF-α inhibitors). Statistical analyses were performed to assess long-term efficacy and safety. The cohort included 7 (53.8

This comprehensive review synthesizes the latest advancements in understanding inflammatory disorders affecting cerebral small vessels, a distinct yet understudied category within cerebral small vessel diseases (SVD). Unlike classical SVD, these inflammatory conditions exhibit unique clinical presentations, imaging patterns, and pathophysiological mechanisms, posing significant diagnostic and therapeutic challenges. Highlighting their heterogeneity, this review spans primary angiitis of the central nervous system, cerebral amyloid angiopathy-related inflammation, systemic vasculitis, secondary vasculitis, and vasculitis in autoinflammatory diseases. Key discussions focus on emerging insights into immune-mediated processes, neuroimaging characteristics, and histopathological distinctions. Furthermore, this review underscores the importance of standardized diagnostic frameworks, individualized immunomodulation approaches, and novel targeted therapies to address unmet clinical demands.

AIM:The NLR family pyrin domain containing 3-associated autoinflammatory disease (NLRP3-AID) is a rare and heterogeneous hereditary inflammatory disorder caused by variants in the NLRP3 gene on chromosome 1q44. This condition encompasses a broad spectrum of clinical phenotypes, including urticarial rash, fever, ocular disorders, hearing loss, and musculoskeletal and central nervous system (CNS) involvement. This study reports the clinical features and newly identified NLRP3 gene variants in two Chinese Han patients with NLRP3-AID presenting with leukoencephalopathy. CASE PRESENTATION:The study includes two adult male patients aged 25 and 24 years. Both patients experienced recurrent fevers with elevated C-reactive protein levels during febrile episodes, which normalized during asymptomatic intervals. Elevated cerebrospinal fluid protein levels and magnetic resonance imaging (MRI) findings of intracranial calcification and white matter damage were observed in both cases. Genetic testing revealed novel heterozygous NLRP3 variants: p.L798M in Patient 1 and p.K829T in Patient 2. Both patients received treatment with adalimumab and canakinumab, resulting in significant clinical improvement. RESULTS:The clinical and genetic features of two NLRP3-AID patients were characterized. Functional studies demonstrated overactivation of the NLRP3 inflammasome in these patients. CONCLUSIONS:Neurological involvement in NLRP3-AID patients is variable. This study expands the clinical spectrum of CNS damage in NLRP3-AID to include intracranial calcification and leukoencephalopathy. Additionally, two novel NLRP3 variants, L798M and K829T, were identified and associated with the disease.

Behçet's disease (BD) is a life-threatening systemic vasculitis characterized by polymorphonuclear neutrophils (PMN) and macrophage activation. However, the interaction of PMN and macrophages remains elusive. To elucidate the potential dysregulation of BD PMN exosomes on macrophage activation, PMN exosomes from both BD patients and healthy controls are isolated, quantified and incubated with macrophages. We find that BD PMN exosomes are decreased and negatively correlated with C-reactive protein (CRP). PMN exosomes can suppress IL-6, TNF, CD80 and CD86 expressions on macrophages, which are attenuated in BD PMN exosomes. In addition, by miRNA sequencing of PMN exosomes, RNA sequencing of miRNA-transfected macrophages, and dual luciferase reporter assay validation of the miRNA target, we find that miR-122-5p is decreased in BD PMN exosomes, targeting IRF5, suppressing TLR4 signaling and IFN-β autocrine, eventually downregulating macrophage activation. Our study illustrates that BD PMN exosomes are decreased in both quantity and miR-122-5p, which impairs the potential immunoregulatory effects on macrophages through degrading IRF5 and suppressing IFN-β autocrine, shedding light on the interaction mechanism between PMN and macrophages.

Interleukin (IL)-17, a pro-inflammatory cytokine, plays a pivotal role in immune regulation by bridging innate and adaptive responses. Beyond its canonical involvement in T helper-17 cells-mediated immunity, IL-17 contributes significantly to the pathogenesis of systemic autoinflammatory diseases (SAIDs) including Familial Mediterranean Fever (FMF), nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3)-associated autoinflammatory diseases, and synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome. Dysregulated IL-17 signaling drives inflammasome activation, neutrophil recruitment, and chronic tissue inflammation. IL-17 inhibitors have demonstrated efficacy in refractory SAIDs, though challenges such as increased infection risks, paradoxical inflammatory reactions, and uncertainties regarding long-term safety persist. Currently, there is insufficient data to support the use of IL-17 inhibitors as first-line treatments, and their role in managing SAIDs is yet to be fully defined. This review highlights the mechanistic role of IL-17 in SAIDs and emerging therapeutic strategies, including IL-17-targeted monotherapies and combination approaches with IL-1 or tumor necrosis factor (TNF) inhibitors. Future research should focus on biomarker development, combination therapies, and long-term studies to optimize the safety and efficacy of IL-17-targeted therapies in SAIDs.

•We reported a Chinese pedigree of PAAND with two affected members, with MEFV P369S and R408Q variants in cis.•The patients were successfully treated with IL-1 inhibitor canakinumab.•Our clinical and functional data confirmed the heterogeneity of MEFV P369S/R408Q variants, and we speculated they might be associated with PAAND.

Objectives: Nucleotide-binding oligomerization domain-like receptor family, pyrin domain containing 3-associated autoinflammatory disease (NLRP3-AID) is a rare autosomal dominant systemic autoinflammatory disease. We aimed to summarize the phenotypic and genotypic features of Chinese adult NLRP3-AID patients with hearing loss. Methods: A retrospective cohort study of twenty-one adult patients with NLRP3-AID was conducted in Peking Union Medical College Hospital between July 2015 and March 2023. All patients underwent whole exome sequencing and otorhinolaryngologic assessments. Clinical features and therapeutic data were collected and analysed. Results: We found that 13/21 (61.90%) of patients had hearing loss with high-frequency impairment in the majority, and most patients presented with vestibular dysfunction as a new finding. The NLRP3-AID patients with early-onset, cold or stress triggered episodes, red eyes, fatigue, hypopsia and mutations located in the NACHT domain of the NLRP3 protein were more likely to suffer from hearing loss, especially sensorineural hearing loss, perhaps as a result of pathogenic variants of high penetrance. By a series of audiological evaluations, TNF-alpha inhibitors were confirmed to improve or reverse hearing loss. Conclusions: We reported the first cohort of Chinese adult NLRP3-AID patients with hearing loss and characterized vestibular dysfunction, highlighted the necessity for attention to high-frequency hearing and provided potential alternative treatment.

Objective To investigate the optic disc changes (ODC) in Chinese patients with NLRP3-associated autoinflammatory disease (NLRP3-AID).Methods Patients who were diagnosed with NLRP3-AID at the Department of Rheumatology, Peking Union Medical College Hospital between April 2015 and December 2022 were retrospectively reviewed and analyzed.Results A total of 20 patients were enrolled in this retrospective study. All 20 patients had a moderate MWS NLRP3-AID phenotype. Thirteen patients (65%) had ocular involvements. The interval between symptoms onset and diagnosis was significantly longer in patients with ocular involvement than in patients without (p = 0.044). The incidence of hearing loss was significantly higher in patients with ocular involvement (p = 0.017), while the incidence of abdominal pain was significantly lower when compared to patients without ocular involvement (p = 0.007). Optic disc swelling (ODS) (50%) was the most common ODC. All of the four T348M mutation carriers within our cohort exhibited ODS with visual-field defects. There was a significant difference between patients with/without ODS regarding the number of patients carrying T348M mutation (p = 0.014). The occurrence of hearing loss and CNS involvement was significantly higher in the group with ODS compared to the group without (p = 0.0014, p = 0.0198). Of the eight patients who underwent lumbar puncture, five presented with intracranial hypertension (IH). ODS was observed in all patients with IH. The serum inflammatory markers were significantly higher in patients with ODS than in those without. Two patients receiving regular subcutaneous IL-1 inhibitor treatment showed improvements in ODC.Conclusions ODC is common among Chinese patients with NLRP3-AID, with ODS being the most common manifestation. Hearing loss and CNS involvement often accompany the occurrence of ODS. The serum inflammatory markers are associated with ODS. The T348M mutation is more likely to lead to ODC with visual-field defects.

Background and objectives The study investigated the pathogenesis of Yao syndrome (YAOS), a rare systemic autoinflammatory disease associated with the nucleotide-binding oligomerization domain containing 2 ( NOD2 ) gene variants. Methods RNA sequencing analyses were used to detect transcriptomic profile changes. Immunoblot and immunohistochemistry were used to examine the NOD2-mediated inflammatory signaling pathways and ELISA was used to detect cytokines. Results Transcriptome analysis of YAOS revealed NOD-like receptor signaling pathway enrichment. Compared with HCs, P-RIP2, p-p65, p-p38, p-ERK, and p-JNK notably increased in PBMCs of a patient with YAOS. P-RIP2, p-p65, and p-p38 elevated in small intestinal mucosa tissues. P-p65 and p-p38 in synovial tissues from YAOS were higher than those in patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Serum interleukin (IL)-6 level along with tumor necrosis factor (TNF)-α and IL-6 secreted from PBMCs were markedly higher in patients with YAOS in comparison to healthy controls (HCs). The supernatants of synovial cells from a patient with YAOS showed substantially higher IL-1β and IL-6 levels than those of RA and OA. Canakinumab therapy of a Q902K heterozygous patient with YAOS resulted in notable clinical improvement. Conclusion Overproduction of pro-inflammatory cytokines and the hyperactivation of NOD2-mediated signaling pathways were found in the NOD2 variant Q902K patient with YAOS. NOD2-RIP2-MAPK pathway might play a pivotal role in the pathogenesis of YAOS. These results provide new perspectives for targeted therapies in YAOS.

Background:Lung cancer is a common malignant tumor, which is seriously harmful to human life and health. Nowadays, it has gradually become one of the best treatments for non-small cell lung cancer (NSCLC) to combine immunotherapy and chemotherapy, and its clinical efficacy is preliminary. Nevertheless, substantial differences exist between various studies and various indicators. Despite their unconvincing results, high-quality research evidence is needed to support them. In this case, further correlative studies are necessary to investigate the prognostic outcomes of PD-1/PD-L1 suppressors in combination with chemotherapeutic drugs in NSCLC. Methods:The online public databases were searchable for the clinical trials that consisted of NSCLC patients who had concluded their chemotherapy and who had accepted PD-1/PD-L1 suppressors. The time-span of the search spanned from the beginning to the end of the database. Two investigators retrieved the data independently. RevMan 5.3 statistical software was utilized for the assessment of bias risk. The software followed the Cochrane Handbook 5.3 guidelines. Results:There were seven clinically controlled studies with 2781 NSCLC samples finally included in this study. A meta-analysis of the post-treatment overall response rate (ORR) was undertaken. A remarkably higher ORR rate was observed in the study group (p<0.05). Study participants had a noticeably longer PFS (HR=0.61, 95% CI=0.54-0.70, P<0.00001). Study participants had markedly longer overall survival (OS) (HR=0.651, 95% CI=0.52-0.82, P<0.05). The incidence of adverse events (AEs) of Grade 3 or above was not clinically clearly different (P>0.05), as demonstrated by the incidence of AEs. The funnel plots were separately charted in accordance with ORR rate, PFE, OS, and Grade 3 AEs. The majority of the funnel plots were symmetrical and a minority of funnel plots were asymmetrical, indicating the heterogeneity of research and the limited evidence available may lead to some publication bias in the contained literature. Conclusion:The combined PD-1/PD-L1 inhibitors with conventional chemotherapy can dramatically elevate the prognosis of NSCLC patients, obviously enhancing the ORR rate and prolonging their PFS and OS. Furthermore, it was found that adding PD-1/PD-L1 inhibitors to conventional chemotherapy did not result in any additional adverse effects.

NLRP3-associated autoinflammatory disease (NLRP3-AID) is a spectrum of autosomal dominant inherited diseases associated with NLRP3 gene mutations. Reports of Chinese NLRP3-AID cases are limited to date. In the present study, we aim to describe the phenotype and genotype of a cohort of Chinese adult NLRP3-AID patients This single-center study included sixteen adult patients diagnosed with NLRP3-AID at Department of Rheumatology, Peking Union Medical College Hospital from April 2015 to September 2021. Whole-exome sequencing using next-generation sequencing was performed in each patient. Clinical data and mutational information were compared with a European cohort. The median age of disease onset was 16 (0–46) years old, and adult-onset was observed in 4 patients (25

Background:Blau syndrome (BS) is a monogenic disorder caused by NOD2 gene variants characterized by the triad of granulomatous polyarthritis, rash, and uveitis. Atypical symptoms were recognized in one-third to one-half of individuals with BS. This study aims to describe the clinical features of BS patients with hypertension and digestive system involvement.Methods:The complete clinical data of a BS patient complicated with hypertension and hepatic granulomas were collected and documented. We also performed a literature search to find all reported cases of BS with hypertension and digestive system involvement.Results:We reported the case of a 19-year-old man who presented with early onset symmetric polyarthritis and hypertension at age 5 and hepatic granulomas and cirrhosis at age 19. He was diagnosed with BS by the finding of a variant of the NOD2 gene (R334W). Through the literature review, 24 patients with BS were found who were reported to have hypertension, and 38 patients were found who had different digestive system manifestations such as hepatic granulomas, hepatosplenomegaly, diverticulitis, and intestinal granuloma. Among the 38 BS patients with digestive system involvement, 14 had hepatic granulomas proven by liver biopsy.Conclusions:Hypertension and digestive system involvement are rare manifestations of BS. Clinicians, especially rheumatologists, must be aware of atypical symptoms of BS.