PULMONARY PATHOLOGIES AND MANAGEMENT STRATEGIES IN PRIMARY IMMUNODEFICIENCIES

pulmonary_pathologies_kapak

FUNGAL AND MYCOBACTERIAL PULMONARY INFECTIONS IN PRIMARY IMMUNODEFICIENCIES

Mehmet Emin Gerek

Konya Necmettin Erbakan University, Faculty of Medicine, Department of Immunology and Allergic Diseases, Konya, Türkiye

Gerek ME. Fungal and Mycobacterial Pulmonary Infections in Primary Immunodeficiencies. In: Arslan Ş editor. Pulmonary Pathologies and Management Strategies in Primary Immunodeficiencies. 1st ed. Ankara: Türkiye Klinikleri; 2025. p.45-59.

ABSTRACT

Primary immunodeficiencies (PIDs) are rare disorders caused by genetic mutations affecting various immune system components. These defects render individuals particularly susceptible to a broad range of infections, notably those caused by fungal and mycobacterial pathogens. Dysregulations in interleukin-17 (IL-17) and interferon-gamma (IFN-g) pathways significantly impair host defense mechanisms against Candida, Aspergillus species, and mycobacteria. Defects in the IL-17 pathway are linked to mucosal candidiasis, while mutations in CARD9 contribute to both mucosal and invasive fungal infections. Similarly, abnormalities in the interleukin-12/23 (IL-12/23)–IFN-g axis underlie Mendelian susceptibility to mycobacterial diseases (MSMD), a rare yet severe clinical entity. This chapter provides a comprehensive overview of epidemiology, pathophysiology, clinical manifestations, diagnostic approaches, and therapeutic strategies related to monogenic PIDs predisposing fungal and mycobacterial infections. The infection spectrum and treatment responsiveness associated with genetic defects such as Chronic Granulomatous Disease (CGD), signal transducer and activator of transcription 1/3 (STAT1/STAT3) mutations, interleukin-12 receptor subunit beta-1 (IL12RB1), interferon-gamma receptor 1 (IFNGR1), and tyrosine kinase 2 (TYK2) are thoroughly discussed. Diagnostic strategies incorporate biomarkers like galactomannan and beta-D-glucan, advanced imaging techniques such as high-resolution computed tomography (HRCT) and positron emission tomography–computed tomography (PET-CT), and genetic analyses. Treatment includes targeted antifungal and antimycobacterial agents and immunomodulatory and curative approaches, such as recombinant IFN-g therapy and hematopoietic stem cell transplantation (HSCT). Preventive measures encompass prophylactic treatments, environmental control strategies, genetic screening programs, and vaccination efforts, which are particularly important for high-risk populations in reducing infection burden. Emerging advancements in gene-editing technologies, artificial intelligence–assisted diagnostic platforms, and the integration of international surveillance data herald a new era in managing PID-associated infections.

Keywords: Primary immunodeficiency; Fungal pulmonary infections; Mycobacterial pulmonary infections; IL-17/CARD9 pathway; IL-12/IFN-g axis; Chronic Granulomatous Disease (CGD); Mendelian Susceptibility to Mycobacterial Disease (MSMD)

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