Severe Opportunistic Infections Without a Monogenic Defect: Clues to a Phenocopy?
Year: 2025
Type: article
Study design: Case Report
Abstract: Background Diagnosing phenocopies of inborn errors of immunity is challenging due to broad and nonspecific clinical presentations. Patients exhibit severe, recurrent, or opportunistic infections that mimic monogenic immune defects but lack identifiable genetic variants. Therefore, diagnosis may be delayed or missed altogether. Here, we describe an adult case of progressive immunodeficiency features without known monogenic cause, raising suspicion for an acquired etiology, including anti–interferon-gamma autoantibodies. Case Presentation A 31-year-old Brazilian male, HIV-negative, was first admitted with fatigue, weight loss, dyspnea, and fever. X-ray showed an important lung lesion, and pulmonary cryptococcosis with central nervous system dissemination was diagnosed. During hospitalization, the patient presented COVID-19, which evolved with multiple complications, namely, secondary sclerosing cholangitis, stroke, peripheral polyneuropathy, and renal failure requiring hemodialysis. He was hospitalized for 7 months and also developed herpes zoster and a sacral ulcer complicated with osteomyelitis (due to K. pneumoniae). Afterwards, he was periodically hospitalized to treat urinary and bronchopulmonary infections with IV antibiotics. Eight months after discharge, he presented hemoptysis and was diagnosed with bacilliferous pulmonary tuberculosis. Dihydrorhodamine (normal) and immunoglobulin testing (IgA 113; IgM 55; IgG 1,246; IgE 373) were performed. Immunophenotyping of peripheral blood: CD3 658 (83.7%); CD4 432 (54.9%); CD8 179 (22.8%); CD4-/CD8- 6%; lymph B: CD19 63 (8%); natural killer lymph [CD56+/CD3-]: 65 (8%). No family history of immune diseases was reported. Exome sequencing was negative for pathogenic variants that would justify phenotype. Discussion Given the patient’s atypical infectious profile, absence of pathogenic variants on exome sequencing, and preserved basic immune parameters, a nongenetic immune dysregulation is suspected. We plan to investigate anti–IFN-γ autoantibodies, which could confirm a phenocopy of Mendelian susceptibility to mycobacterial disease. This case underscores the importance of considering phenocopies in the differential diagnosis of adult-onset infectious syndromes with no identifiable monogenic defect.
Source: Journal of Human Immunity
Authors: Helena Ashton Prolla, Laura Boueri Ticle Lima, Martina Schroeder Wissmann, Mayara Jorgens Prado, Leonardo Navarrina, Nathan Araujo Cadore, Renan Cesar Sbruzzi, Laurinda Medeiros Ramalho, Paul Bastard, Anne Puel, Jacinta Bustamante, Jean-Laurent Casanova, Osvaldo Artigalás, Fernanda Sales Luiz Vianna
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: diamond
OpenAlex ID: W7116745548
FWCI:
Cites:
Cited by:
Related to: