Secondary hypogammaglobulinemia in adults—A large retrospective cohort study / Hipogammaglobulinemia secundaria en adultos: estudio de cohorte retrospectiva

Background and objective: IgG replacement therapy (IgG-RT) has radically changed the clinical evolution of primary immunodeficiencies, yet the information regarding secondary hypogammaglobulinemia (SHG) is insufficient or conflicting. We aim to describe clinical features, evolution and treatment of SHG patients in our center. Methods: Dynamic retrospective cohort between January 2001 and July 2021 of adults with gamma globulin fraction <0.6g/dL in a serum protein electrophoresis and a coincident decrease of IgG levels – with a disease-related SHG or treatment that reduces serum immunoglobulins. Results: We included 1012 patients with SHG with a median follow-up of 5 years (IQR 2–8). Hematological diseases were identified in 95% of the patients and 61% received drugs related to SHG. Sixty five percent had more than one etiological factor associated with SHG. Infectious diseases were present in 69% of the patients, 48% had respiratory infections and 17% had severe infections. There was statistical association between respiratory and severe infections with multiple myeloma (MM), lymphoma and rituximab. MGUS had less infections and death compared with other etiologies. IgG-RT was indicated in 18.7% of the patients and 4.6% received it for more than 6 months with variable intervals. Among the latter group, there was a significant reduction of all-type infections and respiratory infections with IgG-RT (p<0.001), and it was consistent with similar findings in lymphoma, MM and all IgG levels subgroups. Conclusion: SHG was associated with more than one etiological factor and a high frequency of infections. IgG-RT indication was irregular yet still effective. It is relevant to consider IgG levels screening, monitoring and accurate indication of IgG-RT.(AU)

Antecedentes y objetivos: La IgG sustitutiva ha cambiado radicalmente la evolución de las inmunodeficiencias primarias, mientras que la información sobre hipogammaglobulinemia secundaria (HGS) es insuficiente y discordante. El objetivo del estudio es describir las características clínicas, evolución y tratamiento de pacientes con HGS. Métodos: Cohorte retrospectiva dinámica entre enero de 2001 y julio de 2021 de adultos con proteinograma y fracción de gammaglobulina <0,6g/dL y dosaje disminuido de IgG, con enfermedad o tratamiento que produzcan HGS. Resultados: Se incluyó a 1.012 pacientes con HGS con una mediana de seguimiento de 5 años (IIC 2-8). El 95% tenía enfermedad hematológica y el 61% recibió fármacos asociados a HGS. El 65% tenía más de un factor etiológico asociado con HGS. El 69% presentó infecciones de cualquier tipo, el 48% infecciones respiratorias y el 17%, infecciones graves. Hubo asociación significativa entre infecciones respiratorias y graves entre los subgrupos de mieloma múltiple, linfoma y rituximab. Los pacientes con MGUS tuvieron menor frecuencia de infecciones y muerte comparados con otros factores etiológicos. El 18,7% de los pacientes recibió IgG sustitutiva y el 4,6% de forma crónica, con intervalos variables. Los últimos tuvieron disminución significativa de infecciones de cualquier tipo e infecciones respiratorias con IgG sustitutiva (p<0,001), que se mantuvo en los subgrupos con mieloma múltiple, linfoma y todos los niveles de IgG. Conclusión: La HGS asoció más de un factor etiológico y alta frecuencia de infecciones. La indicación de IgG sustitutiva fue irregular, pero, aún así, efectiva. Se plantea considerar el dosaje de inmunoglobulinas, monitoreo y la adecuada indicación de IgG sustitutiva.(AU)

Secondary hypogammaglobulinemia in adults-A large retrospective cohort study.

BACKGROUND AND OBJECTIVE: IgG replacement therapy (IgG-RT) has radically changed the clinical evolution of primary immunodeficiencies, yet the information regarding secondary hypogammaglobulinemia (SHG) is insufficient or conflicting. We aim to describe clinical features, evolution and treatment of SHG patients in our center. METHODS: Dynamic retrospective cohort between January 2001 and July 2021 of adults with gamma globulin fraction <0.6g/dL in a serum protein electrophoresis and a coincident decrease of IgG levels - with a disease-related SHG or treatment that reduces serum immunoglobulins. RESULTS: We included 1012 patients with SHG with a median follow-up of 5 years (IQR 2-8). Hematological diseases were identified in 95% of the patients and 61% received drugs related to SHG. Sixty five percent had more than one etiological factor associated with SHG. Infectious diseases were present in 69% of the patients, 48% had respiratory infections and 17% had severe infections. There was statistical association between respiratory and severe infections with multiple myeloma (MM), lymphoma and rituximab. MGUS had less infections and death compared with other etiologies. IgG-RT was indicated in 18.7% of the patients and 4.6% received it for more than 6 months with variable intervals. Among the latter group, there was a significant reduction of all-type infections and respiratory infections with IgG-RT (p<0.001), and it was consistent with similar findings in lymphoma, MM and all IgG levels subgroups. CONCLUSION: SHG was associated with more than one etiological factor and a high frequency of infections. IgG-RT indication was irregular yet still effective. It is relevant to consider IgG levels screening, monitoring and accurate indication of IgG-RT.

CD40 Ligand Deficiency in Latin America: Clinical, Immunological, and Genetic Characteristics.

CD40 ligand (CD40L) deficiency is a rare inborn error of immunity presenting with heterogeneous clinical manifestations. While a detailed characterization of patients affected by CD40L deficiency is essential to an accurate diagnosis and management, information about this disorder in Latin American patients is limited. We retrospectively analyzed data from 50 patients collected by the Latin American Society for Immunodeficiencies registry or provided by affiliated physicians to characterize the clinical, laboratory, and molecular features of Latin American patients with CD40L deficiency. The median age at disease onset and diagnosis was 7 months and 17 months, respectively, with a median diagnosis delay of 1 year. Forty-seven patients were genetically characterized revealing 6 novel mutations in the CD40LG gene. Pneumonia was the most common first symptom reported (66%). Initial immunoglobulin levels were variable among patients. Pneumonia (86%), upper respiratory tract infections (70%), neutropenia (70%), and gastrointestinal manifestations (60%) were the most prevalent clinical symptoms throughout life. Thirty-five infectious agents were reported, five of which were not previously described in CD40L deficient patients, representing the largest number of pathogens reported to date in a cohort of CD40L deficient patients. The characterization of the largest cohort of Latin American patients with CD40L deficiency adds novel insights to the recognition of this disorder, helping to fulfill unmet needs and gaps in the diagnosis and management of patients with CD40L deficiency.