CHILDHOOD MASTOCYTOSIS NEW DEVELOPMENTS IN DIAGNOSIS AND TREATMENT

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CHILDHOOD MASTOCYTOSIS AND HYPOGAMMAGLOBULINEMIA

Fatih Çelmeli

University of Health Science, Antalya Education and Research Hospital, Department of Pediatric Immunology and Allergy, Antalya, Türkiye

Çelmeli F. Childhood Mastocytosis and Hypogammaglobulinemia. In: Özdemir Ö, editor. Childhood Mastocytosis: New Developments in Diagnosis and Treatment. 1st ed. Ankara: Türkiye Klinikleri; 2025. p.219-226.

ABSTRACT

Childhood mastocytosis is a rare and heterogeneous disorder characterized by the abnormal prolifera- tion and accumulation of mast cells in various tissues, most prominently in the skin, where it manifests as cutaneous mastocytosis. This condition is generally self-limiting and often resolves spontaneously by puberty. However, emerging evidence indicates that mastocytosis can have complex and signifi- cant effects on the immune system, potentially leading to hypogammaglobulinemia in pediatric pa- tients. Hypogammaglobulinemia, characterized by decreased levels of immunoglobulins in the serum, can occur transiently in some cases of childhood mastocytosis, complicating disease management by increasing susceptibility to infections and influencing the development of autoimmune conditions. The pathophysiological connections between childhood mastocytosis and hypogammaglobulinemia are complex and multifaceted, involving mast cell activation, genetic mutations, and their impact on B-cell development and function. Excessive mast cell activation, driven by mutations such as those in the c-KIT gene (e.g., c-KIT D816V mutation), leads to constitutive activation of the c-KIT receptor tyrosine kinase. This aberrant activation triggers downstream signaling cascades that promote mast cell proliferation, survival, and mediator release. The mediators secreted by hyperactivated mast cells, including cytokines such as Transforming Growth Factor Beta 1 (TGF-b1) and interleukin-6 (IL-6), can suppress immunoglobulin synthesis by inhibiting B-cell differentiation and class-switch recombi- nation. These detrimental effects on humoral immunity may result in decreased levels of immunoglob- ulins, particularly immunoglobulin G (IgG) and immunoglobulin M (IgM), thereby contributing to the development of hypogammaglobulinemia. This chapter provides a comprehensive examination of the molecular mechanisms underlying the relationship between childhood mastocytosis and hypogamma- globulinemia, focusing on the roles of mast cell activation, genetic mutations, and the influence of mast cell mediators on B-cell development and immunoglobulin production. It further explores the clinical implications of this interplay, emphasizing the importance of recognizing hypogammaglobulinemia in patients with mastocytosis for improved diagnosis, monitoring, and personalized treatment strat- egies. Understanding this complex relationship is essential for optimizing patient outcomes, guiding immunization practices, and informing future research aimed at developing targeted therapies that address both mast cell dysregulation and immune deficiencies while minimizing adverse effects on overall immune function.

Keywords: Childhood mastocytosis; Hypogammaglobulinemia; Mast cell activation; B-cell development and function

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