Variable Phenotypic Expression of an X-Linked Recessive Lymphoproliferative Syndrome

Purtilo, David T.; DeFlorio, Daniel; Hutt, Lindsey M.; Bhawan, Jag; Yang, James P. S.; Otto, Ralph N.; Edwards, William

doi:10.1056/nejm197711172972001

Cited by 238 publications

(59 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We have studied six members of a previously reported family (5) who illustrate the natural history of the immunodeficiency observed in males affected with XLP. In this kindred, 20 males have been affected with XLP (5). Two mem-I Abbreviations used in this paper: AK, anomalous killer; anti-Ig, anti-immunoglobulin-coated beads; Con A, concanavalin A; EA, early antigen; EBNA, Epstein-Barr nuclear antigen; EBV, Epstein-Barr virus; LCL, lymphoblastoid cell lines; MLR, mixed lymphocyte reaction; NK, natural killer; PHA, phytohemagglutinin; PWM, pokeweed mitogen; SGOT, serum glutamic oxaloacetic transaminase; VCA, viral capsid antigen; XLP, X-linked lymphoproliferative syndrome.…”

mentioning

confidence: 99%

X-linked lymphoproliferative syndrome. Natural history of the immunodeficiency.

Sullivan¹,

Byron²,

Brewster³

et al. 1983

J. Clin. Invest.

118

View full text Add to dashboard Cite

A B S T R A C T The X-linked lymphoproliferative syndrome is characterized by immunodeficiency to Epstein-Barr virus (EBV) manifested by severe or fatal infectious mononucleosis and acquired immunodeficiency. We studied immune responses in six males of a well-characterized kindred with the X-linked lymphoproliferative syndrome. Two males were studied before and during acute fatal EBV infection. Both individuals demonstrated normal cellular and humoral immunity before EBV infection. During acute EBV infection, both individuals developed vigorous cytotoxic cellular responses against EBV-infected and -iipinfected target cells. Anomalous killer and natural killer T cell activity was demonstrated against a va'-riety of lymphoid cell lines, autologous fibroblasts and autologous hepatocytes. Effector cells responsible for anomalous killing reacted with a pan-T cell monoclonal antibody, and belonged to the OKT.8 T cell subset. Death in each case was caused by liver failure, but one patient developed extensive liver necrosis, whereas the other developed a massive infiltration of the liver with EBV-infected immunoblasts after aggressive immunosuppressive therapy. Immunological studies were performed on four males who had survived EBV infection years previously. They demonstrated global cellular immune defects with deficiencies of lymphocyte proliferative responses to mitogens and antigens, humoral immune deficiencies, abnormalities of regulatory T cell subsets and deficient natural killer cell activity. We propose that an aberrant immune response triggered by acute EBV infection results in unregulated anomalous killer and natural killer cell activity against EBV infected and uninfected cells. These studies suggest that global immune defects appearing in males with X-linked lymphopro-

show abstract

mentioning

confidence: 99%

X-linked lymphoproliferative syndrome. Natural history of the immunodeficiency.

Sullivan¹,

Byron²,

Brewster³

et al. 1983

J. Clin. Invest.

118

View full text Add to dashboard Cite

show abstract

“…Recovery is followed by a long-lasting and generally asymptomatic latent state of infection (7,39,40). Suppression of the normal immune response by agents such as cyclosporin A (26) or an anti-T cell monoclonal antibody (27) and suppression in association with congenital or acquired immunodeficiencies (18,19,25) have, however, resulted in the emergence of EBV-induced malignancies.…”

Section: Discussionmentioning

confidence: 99%

“…This has been attributed to the vigorous host immune response, consisting ofactivated suppressor (8-1 1) and/or cytotoxic T cells (12)(13)(14)(15)(16)(17), that develops during the course of the disease. Patients with a congenital disorder of this immune response, referred to as the X-linked lymphoproliferative syndrome, experience fatal episodes of infectious mononucleosis (18,19).…”

Section: Introductionmentioning

confidence: 99%

Suppressor T cell clones from patients with acute Epstein-Barr virus-induced infectious mononucleosis.

Wang¹,

Blaese²,

Zoon³

et al. 1987

J. Clin. Invest.

View full text Add to dashboard Cite

Suppression and/or cytotoxicity are believed to play an important role in the defense against Epstein-Barr virus (EBV) infection. To analyze the role of suppressor T cells in relation to EBV, we sought to clone and study these T cells. Analysis of 152 T cell clones derived from the peripheral blood of two patients with acute EBV-in4uced infectious mononucleosis (IM) yielded 11 highly suppressive clones that had no cytotoxic activity for the natural killer sensitive K562 cell line, an autologous EBV-infected cell line, or an allogeneic EBV-infected B cell line. Four of six suppressor T cell clones also profoundly inhibited EBVinduced immunoglobulin production, and five of five clones delayed the outgrowth of immortalized cells. These results indicate that during acute IM, suppressor T cells capable of inhibiting B cell activation in the absence of cytotoxicity can be identified, and may play a key role in the control of EBV infection.

show abstract

“…In this six-generation pedigree at least 19 males died of XLP. 1,10 The patient from the GL01 family ( Figure 2) was admitted to the Gaslini Institute (Genova) at the age of 6 years for fever, hepatosplenomegaly and persistent high levels of transaminase enzymes after an EBV infection. The liver and bone marrow biopsies suggested the presence of a lymphoproliferative disease.…”

Section: Patients and Familiesmentioning

confidence: 99%