Studies Of Primary Immunodeficiency Diseases

Niaid Extramural Activities

Investigators

Linked publications & trials

Abstract

Members of the Mucosal Immunity Section continue to actively follow a large cohort of patients with common variable immunodeficiency (CVI) and IgA deficiency. In addition, they follow patients with related immunodeficiency states including those with intestinal lymphangiectasia, Good?s syndrome, hyperIgM syndrome and X-linked agammaglobulinemia. Selected members of this cohort are subject to basic studies of their underlying disorder and to clinical studies of their consequences of their immunodeficiency. One active protocol (Clinical Protocol 01-1-0153) involving the CVI and IgA deficiency patients is an on-going study designed to better understand the nature of GI problems developing in a substantial subset of these patients. This consists of a syndrome characterized by malabsorption and weight loss due to partial intestinal villus atrophy that, some cases, can be severe enough to lead to progressive inanition requiring parental therapy to stave off death. The study consists of the clinical and immunological evaluation of patients, including the collection of duodenal biopsies by endoscopy and then the isolation of lamina propria cells to determine their capacity to secrete cytokines. Our hypothesis is that patients develop an autoimmune inflammation of the gastrointestinal mucosa and thus secrete inflammatory cytokines such as TNF-a. Thus, this syndrome may be amenable to currently available anti-TNF-a medications. To date, we have completed studies of 3-5 patients with CVI and have obtained promising data that our hypothesis is indeed correct. In a second active protocol (Clinical Protocol 02-C-0009) we conducted in association with Dr. David Nelson of the Cancer Institute, a Phase 1 trial of a possible therapeutic agent for the treatment of IgA deficiency, namely BlyS. The latter is an experimental agent produced by Human Genome Sciences that is a member of the TNF-receptor family that has been shown to stimulate B cell Ig synthesis in both studies of rodents and primates. The study in question is a sole site Phase 1 study designed to determine the toxicity of BlyS in patients with IgA deficiency. This study has recently been completed in that we have enrolled 15 patients with IgA deficiency; no obvious toxicity has been encountered. We are now in a position to enter a Phase 2 study designed to evaluate the efficacy of BlyS.