D2.371 - Hematologic Findings in Primary Immunodeficiency Disorders: A Single-Center Experience

Primary immunodeficiency disorders (PIDs) are heterogeneous diseases associated with recurrent infections, autoimmunity, lymphoproliferation, and malignancies. Hematological manifestations, particularly autoimmune cytopenias, are common and may represent the initial presentation. This study aimed to evaluate hematological involvement in adult PID patients and its clinical and immunological associations.

Adult patients (≥18 years) with a confirmed diagnosis of PID were retrospectively analyzed. Demographic characteristics, clinical and hematological manifestations, laboratory parameters, and autoimmune or lymphoproliferative involvement were evaluated. Patients with secondary immunodeficiencies were excluded. Statistical analyses were performed using SPSS version 25.0, and p <0.05 was considered statistically significant.

Sixty patients were included (median age: 28 years; 55% male), with a mean diagnostic delay of 9.7 years. Most patients (70%) presented with infections; at diagnosis, six patients had autoimmune manifestations and one patient had lymphoproliferation, while during follow-up, 12 patients (20%) developed at least one episode of autoimmune cytopenia, and lymphoma was observed in two patients (Table 1).

According to the International Union of Immunology Societies phenotypic classification, predominantly antibody deficiency was the most common phenotype, mainly common variable immunodeficiency (65%), followed by X-linked agammaglobulinemia (10%), combined immunodeficiency with syndromic features (12%), diseases of immune dysregulation (7%), immunodeficiency affecting both cellular and humoral immunity (3%), and congenital defects of phagocyte number and/or function (3%).Six patients had concomitant non-hematological autoimmune diseases, including celiac disease, vitiligo, Hashimoto’s thyroiditis, and systemic lupus erythematosus. No significant differences were observed between patients with and without hematological complications regarding pulmonary or gastrointestinal involvement (p=0.382 and p=0.673, respectively). 

CD21^low B-cell levels were significantly higher in patients with autoimmune cytopenia (p=0.025); however, switched memory B-cell and IgG levels were not significantly different. Patients with lymphoproliferation also showed increased CD21^low B-cell levels (p=0.025) and significantly decreased switched memory B-cell levels (p=0.018). IgM levels did not differ according to the presence of lymphoproliferation (p=0.788).

Hematological manifestations, particularly autoimmune cytopenias, are frequent in adult patients with PID. Immunophenotypic abnormalities, including increased CD21^low B-cell levels and altered memory B-cell subsets, are closely associated with autoimmune cytopenias and lymphoproliferation. Early identification of these hematological and immunophenotypic features may improve prognostic assessment and guide patient management.