BACKGROUND: Common variable immunodeficiency (CVID) is characterised by a late onset deficiency of immunoglobulins resulting in recurrent infectious and non-infectious ailments. Most cases are sporadic but occasional familial clustering has been described. We present an extensively affected family with CVID in three consecutive generations. METHODS: We conducted a study in this family to establish clinical phenotype, to clarify the mode of inheritance and to attempt to characterise the immune disturbance by determining immunoglobulin concentrations and B- and T-cell analysis. RESULTS: We describe six patients with CVID in three consecutive generations. In addition, we encountered 10 family members with dysimmunoglobulinemia. B-cell counts were normal, but T-cell analysis showed slightly abnormal results. CONCLUSIONS: The six cases of overt late onset hypogammaglobulinemia are compatible with an autosomal dominant mode of inheritance. The family members with dysimmunoglobulinemia may be at risk to develop overt CVID in the future, in view of the gradual course of progression of the disease in the clinically affected family members. B- and T-cell analysis are inconclusive though may support a possible defect in T-cell function to be involved. To further study this remarkable family and attempt to clarify pathogenesis, we are planning DNA linkage analysis in the near future.
BACKGROUND: Common variable immunodeficiency (CVID) is characterised by a late onset deficiency of immunoglobulins resulting in recurrent infectious and non-infectious ailments. Most cases are sporadic but occasional familial clustering has been described. We present an extensively affected family with CVID in three consecutive generations. METHODS: We conducted a study in this family to establish clinical phenotype, to clarify the mode of inheritance and to attempt to characterise the immune disturbance by determining immunoglobulin concentrations and B- and T-cell analysis. RESULTS: We describe six patients with CVID in three consecutive generations. In addition, we encountered 10 family members with dysimmunoglobulinemia. B-cell counts were normal, but T-cell analysis showed slightly abnormal results. CONCLUSIONS: The six cases of overt late onset hypogammaglobulinemia are compatible with an autosomal dominant mode of inheritance. The family members with dysimmunoglobulinemia may be at risk to develop overt CVID in the future, in view of the gradual course of progression of the disease in the clinically affected family members. B- and T-cell analysis are inconclusive though may support a possible defect in T-cell function to be involved. To further study this remarkable family and attempt to clarify pathogenesis, we are planning DNA linkage analysis in the near future.
Authors: Manfred Fliegauf; Vanessa L Bryant; Natalie Frede; Charlotte Slade; See-Tarn Woon; Klaus Lehnert; Sandra Winzer; Alla Bulashevska; Thomas Scerri; Euphemia Leung; Anthony Jordan; Baerbel Keller; Esther de Vries; Hongzhi Cao; Fang Yang; Alejandro A Schäffer; Klaus Warnatz; Peter Browett; Jo Douglass; Rohan V Ameratunga; Jos W M van der Meer; Bodo Grimbacher Journal: Am J Hum Genet Date: 2015-08-13 Impact factor: 11.025
Authors: Ozgur Kartal; Ugur Musabak; Sait Yesillik; Rahsan I Sagkan; Aysel Pekel; Fevzi Demirel; Abdullah Baysan; Ali Selçuk; Mustafa Güleç; Osman Şener Journal: Wien Klin Wochenschr Date: 2015-04-10 Impact factor: 1.704
Authors: Luis Ignacio Gonzalez-Granado; Raquel Ruiz-García; Javier Blas-Espada; José Manuel Moreno-Villares; Marta Germán-Diaz; Marta López-Nevado; Estela Paz-Artal; Oscar Toldos; Yolanda Rodriguez-Gil; Jaime de Inocencio; Nerea Domínguez-Pinilla; Luis M Allende Journal: Front Immunol Date: 2019-01-29 Impact factor: 7.561