Acquired Agammaglobulinemia after a Life-Threatening Illness with Clinical and Laboratory Features of Infectious Mononucleosis in Three Related Male Children

Abstract

Three males in one family (two siblings and one maternal cousin) had an illness with cervical adenopathy, hepatosplenomegaly, and a fulminant febrile course. In the two survivors agammaglobulinemia developed. One of them became ill at the age of six months and had an Epstein-Barr-virus antibody titer of 1:10 during illness and convalescence. The white-cell count was 120,000 with 90 per cent lymphocytes, most being atypical and forming increased numbers of sheep erythrocyte rosettes. IgM was elevated, IgA normal and IgG decreased. Subsequently, all immunoglobulins were absent, and the Epstein-Barr-virus antibody titer became negative. Peripheral B-cell number remained normal, but abnormal lymph-node architecture associated with failure to respond to antigenic challenge indicated B-cell dysfunction. The pathogenesis of this entity may involve an abnormal T-cell response to transformation of B cells by Epstein-Barr virus, leading to B-cell dysfunction and agammaglobulinemia.

Abnormalities of T cell maturation and regulation in human beings with immunodeficiency disorders.

“…Thus, viral infection would appear to be capable of activating selectively a suppressor population of cells. This is of interest since acquired agammaglobulinemia has been seen to follow a variety of viral infections including infectious mononucleosis (27) The absence of a predominant T cell subset defect in patients with X-linked agammaglobulinemia who lacked circulating surface immunoglobulin bearing cells is consistent with the view that this disease is due to an aberrant differentiation along cells of B, rather than T lineage. However, the observation that patients with both decreased as well as increased inducer/suppressor ratios are frequently detected, suggests that the disease is heterogeneous.…”

Cellular immune controls over Epstein–Barr virus infection: new lessons from the clinic and the laboratory

“…The resultant cytokine storm triggers haemophagocytic lymphohistiocytosis (HLH), leading in most cases to fatal bone marrow failure. Other boys with the same trait present with hypogamma-globulinaemia or B cell lymphoma, conditions that are not linked to (and may precede) EBV infection [66][67][68]. The XLP gene SH2D1A encodes a small adapter protein, SAP, that is expressed in T, NK and i-NKT cells and is involved in the signalling of cell-cell interactions mediated by members of the SLAM family of surface receptors [69] Interestingly, XLP patients have normal numbers of NK and T cells but lack i-NKT cells, fuelling speculation that i-NKT cells may play a role in controlling EBV.…”

Immunophenotypical alterations in a subset of patients with common variable immunodeficiency (CVID)

“…Following Epstein-Barr virus (EBV)-infection activation of suppressor T cells may lead to inhibition of B cell activation [49]. An X-linked familial defect of the surveillance mechanisms of EBV infection has been reported by several others [50,51]. It may also cause a fatal lymphoproliferative syndrome (XLPS), aplastic anaemia, agranulocytosis and hypogammaglobulinaemia.…”