Impact of HIV on Immunoglobulin Levels in CVID

1. Impact of HIV on Immunoglobulin Levels in CVID Lulu Sun Dr. C.M. Tsoukas Common Variable Immune Deficiency (CVID) • A primary immune deficiency • Defined by hypogammaglobulinemia • Males and females equally affected • Many clinical manifestations • B cell numbers normal or reduced • T cell abnormalities common • Pathogenesis not well understood An antigen-bound immunoglobulin molecule HIV-1 • HIV is associated with B cell hyperactivity and elevated blood immunoglobulin levels • polyclonal and virus-specific B cell activation • both nonspecific and specific antibody responses • Mechanism of induction of hypergammaglobulinemia not well understood

2. Patients with Concomitant HIV and CVID A B • There have been published reports of four CVID patients who, upon contracting HIV, had a recovery of immunoglobulin production • We have an HIV patient (13603) whose hypogammaglobulinemia only manifested itself upon anti-retroviral therapy (ART) • suggests HIV was somehow masking the defect that caused low immunoglobulin levels Figure 1. Effect of antiretroviral therapy (ART) on viral load and immunoglobulin levels in a patient with concomitant HIV and CVID.

3. Hypothesis and Methods Hypothesis: • HIV increases immunoglobulin production in CVID patients, possibly by masking a CVID defect in the BAFF signalling pathway • BAFF/BAFFR pathway - B cell survival and homeostasis, isotype switching, Ab responses • Serum BAFF is elevated in HIV patients • Defects in TACI and BAFF-R in CVID patients BAFF Methods: BCMA TACI • 4 subject groups: HIV/CVID patient, HIV patients (high and low viral load), CVID patients, normal controls BAFF-R • Compare: • T cell numbers, B cell numbers, subsets within B cell populations (FACS) • BAFF serum levels (ELISA) • Cell surface molecule expression: BAFF, BAFFR, BCMA, TACI, (FACS) • Cellular proliferation in response to antigens, mitogens, and CD3/CD28 (FACS) • BAFF downstream signaling components: non-canonical NFkB pathway