Absent B-Cells And Decreased T-Cells In A Family With Hypogammaglobulinemia: A Unique Form Of Combined Immune Deficiency?

RATIONALE: We present a fathere and daughter who were initially diagnosed with Common Variable Immune Deficiency (CVID), who were also found to have absent B-cells and low T-cells. This may represent a unique form of Severe Combined Immunodeficiency (SCID).METHODS/RESULTS: The father is a 35-year-old man with a history of CVID diagnosed at age 12 following multiple upper respiratory infections. He was started on intravenous immunoglobulin (IVIG) for hypogammaglobulinemia, but was never admitted for severe infections. His mother and older brother also received gamma globulin for presumed CVID, but both died from infections at age 36. He had one episode of pneumonia at age 19, with occasional sinus infections. His trough IgG level recently was 162, but increased to 724 with higher subcutaneous dosing. His IgA was <7, IgM <0.5, IgE <0.1.The patient's 3-year-old daughter has been receiving IVIG since age 8 months for hypogammaglobulinemia. She also has a history of sinusitis and has never been hospitalized. Her IgA is <7, IgM 6, IgE 0.1. Interestingly, both father and daughter have undetectable B-cells (CD19 <1%) and CD4 lymphopenia–the father's absolute CD4 count was 202, whereas the daughter's CD4 count was 608. Both patients also have low CD8 cell counts (Father: 162, Daughter: 368) and decreased proliferative responses to mitogens and antigens.CONCLUSIONS: This family, along with the deceased relatives, exhibits an unusual pattern of inheritance for B-cell and T-cell deficiency consistent with combined immunodeficiency. Both patients have remained stable on outpatient therapy. Further characterization and investigation of this disease is warranted. RATIONALE: We present a fathere and daughter who were initially diagnosed with Common Variable Immune Deficiency (CVID), who were also found to have absent B-cells and low T-cells. This may represent a unique form of Severe Combined Immunodeficiency (SCID). METHODS/RESULTS: The father is a 35-year-old man with a history of CVID diagnosed at age 12 following multiple upper respiratory infections. He was started on intravenous immunoglobulin (IVIG) for hypogammaglobulinemia, but was never admitted for severe infections. His mother and older brother also received gamma globulin for presumed CVID, but both died from infections at age 36. He had one episode of pneumonia at age 19, with occasional sinus infections. His trough IgG level recently was 162, but increased to 724 with higher subcutaneous dosing. His IgA was <7, IgM <0.5, IgE <0.1. The patient's 3-year-old daughter has been receiving IVIG since age 8 months for hypogammaglobulinemia. She also has a history of sinusitis and has never been hospitalized. Her IgA is <7, IgM 6, IgE 0.1. Interestingly, both father and daughter have undetectable B-cells (CD19 <1%) and CD4 lymphopenia–the father's absolute CD4 count was 202, whereas the daughter's CD4 count was 608. Both patients also have low CD8 cell counts (Father: 162, Daughter: 368) and decreased proliferative responses to mitogens and antigens. CONCLUSIONS: This family, along with the deceased relatives, exhibits an unusual pattern of inheritance for B-cell and T-cell deficiency consistent with combined immunodeficiency. Both patients have remained stable on outpatient therapy. Further characterization and investigation of this disease is warranted.