Prolonged Infections and Inflammatory Diseases in Common Variable Immune Deficiency as a Cause of AA Amyloidosis.

Prolonged Infections and Inflammatory Diseases in Common Variable Immune Deficiency as a Cause of AA Amyloidosis.

Publication date: May 22, 2026

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.

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Concepts Keywords
Amyloid AA amyloidosis
Decades amyloidosis
Immunodeficiency immunodeficiency
Pneumonia
Therapy

Semantics

Type Source Name
disease MESH Infections
disease MESH Common Variable Immune Deficiency
disease MESH AA Amyloidosis
disease MESH inflammation
disease MESH persistent infections
disease MESH osteomyelitis
disease MESH sepsis
disease MESH pneumonia
disease MESH COVID-19
disease MESH nephrotic syndrome
disease MESH proteinuria
disease MESH hypoalbuminemia
disease MESH bronchiectasis
disease MESH bronchiolitis
disease MESH hereditary amyloidosis
disease MESH primary ciliary dyskinesia
disease MESH Amyloidosis
drug DRUGBANK Coenzyme M
disease MESH death
disease MESH heart failure
disease MESH dyspepsia
disease MESH hypertrophic cardiomyopathy
pathway KEGG Hypertrophic cardiomyopathy
disease MESH carpal tunnel syndrome
disease MESH purpura
disease MESH macroglossia
disease MESH infectious diseases
disease MESH aspergillosis
disease MESH cystic fibrosis
disease MESH rheumatoid arthritis
pathway KEGG Rheumatoid arthritis
disease MESH psoriatic arthritis
disease MESH gout
disease MESH Takayasu arteritis
disease MESH syndromes
disease MESH familial Mediterranean fever
disease MESH cryopyrin associated periodic syndrome
disease MESH TRAPS
disease MESH hyperimmunoglobulinemia
disease MESH malignant neoplasms
disease MESH Hodgkin’s lymphoma
disease MESH non Hodgkin’s lymphoma
disease MESH macroglobulinemia
disease MESH HIV infection
pathway REACTOME HIV Infection
disease MESH cyclic neutropenia
disease MESH hyper IgM syndrome
disease MESH hypogammaglobulinemia
disease MESH inflammatory bowel disease
pathway KEGG Inflammatory bowel disease

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