Portal vein thrombosis (PVT) is a rare complication following percutaneous liver biopsy, with an incidence below 0.4% in large multicenter series. We report a 51-year-old male with common variable immunodeficiency (CVID), chronic liver enzyme elevation, and preoperative imaging consistent with cirrhotic morphology, who developed acute abdominal pain within minutes of ultrasound-guided liver biopsy. Notably, biopsy demonstrated only mild steatosis with portal chronic inflammation and no significant fibrosis-a discordance from imaging attributed to CVID-associated nodular regenerative hyperplasia and biopsy sampling error. Contrast-enhanced CT on the day of the procedure showed heterogeneous left lobe enhancement consistent with a transient hepatic attenuation difference (THAD) secondary to focal portal venous obstruction, with a subsegmental filling defect in segment 3 on portal venous phase imaging. Repeat CT on postprocedure day 1 demonstrated thrombus extension into the left main portal vein; MRCP excluded biliary complications and hemobilia. The patient was treated with intravenous heparin transitioned to oral apixaban, with symptomatic improvement and normalization of liver function tests. A formal hypercoagulable evaluation was not performed given the provoked clinical context and normal INR, and no postdischarge imaging was available to assess recanalization; both are acknowledged as limitations. This case illustrates the convergence of multiple risk factors-abnormal hepatic vascular architecture from CVID-related liver disease, endothelial injury from needle passage, and potential hemostatic agent migration-in the pathogenesis of postbiopsy PVT, and underscores the importance of prompt vascular imaging and anticoagulation in patients presenting with acute abdominal pain following liver biopsy.

NFKB2 encodes the precursor p100 which undergoes processing to generate the mature NF-κB2 transcription factor subunit p52. Most of the known pathogenic NFKB2 variants render p100 un-processable and are typically linked to immunodeficiency disorders with antibody deficiency, susceptibility to infections and often autoimmunity. We describe a heterozygous germline NFKB2 missense variant (c.781C>T; R261W) associated with antibody deficiency and recurrent respiratory tract infections in a German family with incomplete penetrance. Patient-derived cells had reduced p52 levels, indicating protein insufficiency as the primary defect. Characterization of the R261W variant in vitro employing overexpression of EGFP-fused wildtype and mutant p100/p52 in HEK293T cells revealed restricted levels of mutant p100, suggesting unsustainable protein expression while maintenance of mutant p52 was almost precluded, confirming a detrimental protein defect. Enforced p100-processing driven by constitutively active NF-κB inducing kinase (NIK) caused subnuclear aggregation of mutant EGFP-p52 while DNA-binding activity was undetectable. Although ectopically over-expressed EGFP-p52-R261W also formed intra-nuclear aggregates - a previously established diagnostic indicator of protein-decaying NFKB1 mutations - its DNA-binding ability was not abolished. In summary, the single amino acid substitution R261W in the N-terminal Rel-homology domain of p100/p52 causes protein loss, particularly of the mature subunit p52. This genetic condition is associated with an inheritable form of hypogammaglobulinemia with mild clinical symptoms. We therefore recommend genetic screening for NFKB2 loss-of-expression variants in mildly affected patients with recurrent respiratory tract infections.

Background/Objectives: AA amyloidosis is a serious complication of chronic inflammation, which may arise in the setting of inborn errors of immunity (IEIs) due to recurrent or persistent infections. Common variable immunodeficiency (CVID) is the most frequent symptomatic IEI in adults, yet its association with secondary AA amyloidosis remains rarely reported. Case presentation: We describe a 37-year-old male with a history of recurrent pneumonia, chronic sinusitis, and osteomyelitis with sepsis since childhood. At age 33, he developed bilateral pneumonia after COVID-19, followed by repeated lower respiratory tract infections. At age 36, nephrotic syndrome (proteinuria 10.69 g/day, hypoalbuminemia) led to kidney and gastric mucosa biopsies, which confirmed AA amyloidosis. Immunological workup revealed panhypogammaglobulinemia (IgG 0.1 g/L, IgA 0.01 g/L, IgM 0.28 g/L), markedly reduced switched memory B cells, and an inverted CD4+/CD8+ ratio. Chest CT showed bronchiectasis, bronchiolitis, and mediastinal lymphadenopathy. Whole-exome sequencing excluded known monogenic IEIs, autoinflammatory, or hereditary amyloidosis genes; a heterozygous likely pathogenic variant in ODAD2 (associated with primary ciliary dyskinesia) was considered incidental. A diagnosis of CVID with secondary AA amyloidosis was established. Conclusions: This case illustrates that CVID may remain undiagnosed for decades and present with secondary AA amyloidosis as the first major complication. In any patient with nephrotic syndrome and a history of recurrent or unusual infections, an IEI should be actively excluded. Early recognition of CVID and appropriate immunoglobulin replacement therapy can prevent infectious exacerbations and potentially halt amyloid progression.

Advances in high-throughput sequencing and genotype-first approaches have revealed a growing number of monogenic autoimmune and autoinflammatory conditions that present in late adolescence or adulthood and sometimes mimic more common rheumatologic diseases. These disorders arise from both germline and somatic mutations and span a broad spectrum of immune dysregulation, including autoinflammation, autoimmunity, immunodeficiency, allergic disease and hematological disorders. Importantly, many affected individuals do not exhibit classical Mendelian inheritance or early-onset disease, instead presenting with incomplete penetrance, variable expressivity or atypical phenotypes that fulfil established classification criteria for diseases such as SLE and vasculitides. In this review, we highlight recently described monogenic immune disorders with relevance to adult rheumatology practice, including germline inborn errors of immunity and somatic mutation-driven conditions. We discuss emerging mechanisms that link innate and adaptive immune dysregulation, clinical features that should prompt genetic evaluation and practical considerations for genetic testing in adult patients. Finally, we examine current challenges and future opportunities in integrating molecular diagnostics into rheumatology care, emphasizing the potential for genetic diagnoses to refine disease classification and inform targeted, mechanism-based therapeutic approaches.

In patients with chronic spontaneous urticaria, especially when it is accompanied by recurrent infections or reduced immunoglobulin levels, analysis for common variable immunodeficiency should be considered. Early diagnosis of common variable immunodeficiency can lead to more effective treatment for the immunodeficiency and its related complications such as chronic spontaneous urticaria.