Long term recovery of IgG and IgM production during HIV infection in a patient with common variable immunodeficiency (CVID)

Abstract

Aims-Commonvariable immunodeficiency (CVID) is the most common serious primary immunodeficiency. This paper describes the immunological consequences of human immunodeficiency virus (HIV) infection in a patient with familial CVID subsequently treated with highly active antiretroviral therapy (HAART). Methods-Serial measurements over 11 years of serum immunoglobulins, specific antibodies to tetanus toxoid and pneumococcal polysaccharides, lymphocyte phenotypes, and HIV viral load were made. Results-The patient recovered total serum IgG and IgM, but not IgA production, with adequate concentrations of specific antibodies, allowing withdrawal of intravenous immunoglobulin without an increase in infections. T cell numbers gradually declined and the patient developed a high grade B cell lymphoma. After successful chemotherapy, HAART was commenced, viral load fell from 472 000 to < 50 copies/ml, and CD4 + T cell numbers increased from 13 to 661 × 10 6 /litre. Antibody production was maintained after suppression of viral load. Conclusions-This is the first definitive report of reversal of IgG and IgM deficiency in familial CVID after HIV infection. Failure to normalise IgA supports the concept of separate predisposing genetic factors for selective IgA deficiency, which when combined with others lead to CVID. Furthermore, a persistently high viraemia is not required to maintain the recovery of immunoglobulin values, suggesting this depends either on a transitory eVect of a high viral load, or a persistence of low amounts of virus. (J Clin Pathol 2001;54:713-715) Keywords: common variable immunodeficiency; human immunodeficiency virus; seroconversion; highly active antiretroviral therapy Common variable immunodeficiency (CVID) is the most common of the primary immunodeficiency disorders requiring immunoglobulin replacement, aVecting about 1/25 000 in the white population. The characteristic feature is severe hypo-immunoglobulinaemia, predominantly aVecting the IgG and IgA classes.

Common variable immunodeficiency and the gastrointestinal tract

“…An interesting phenomenon relates to the recovery of Ig production (mostly IgG and IgM) transiently or permanently following HIV or hepatitis C virus infection (HCV) [16]. These cases suggest that CVID is associated with potentially reversible defects in humoral or cellular immunoregulatory factors and may have some remnant intact backup B-cell system.…”

“…Although CVID may resemble HIV infection in that it can cause weight loss, generalized lymphadenopathy, splenomegaly, diarrhea, and lymphoma, the opportunistic infections characteristic of HIV and AIDS are rare in CVID [16]. Recurrent pyogenic infections of the respiratory tract are the main clinical manifestations of CVID.…”

Recurrent Sinopulmonary Infections in a Patient Whose HIV Masked Common Variable Immunodeficiency

“…Notably, IgA levels remained undetectable in these cases-a finding consistent with the concept that specific immunoregulatory and possibly environmental factors are required to induce CVID in patients with select IgA deficiency. 23 Antiretroviral therapy and subsequent virologic suppression do not appear to effect immunoglobulin production, as two of the above cases demonstrated immunoglobulin recovery and resolution of CVID despite treatment. 22,23 Perhaps the mechanism that leads to polyclonal hypergammaglobulinemia in patients with HIV also leads to immunoglobulin recovery in patients with CVID.…”

“…23 Antiretroviral therapy and subsequent virologic suppression do not appear to effect immunoglobulin production, as two of the above cases demonstrated immunoglobulin recovery and resolution of CVID despite treatment. 22,23 Perhaps the mechanism that leads to polyclonal hypergammaglobulinemia in patients with HIV also leads to immunoglobulin recovery in patients with CVID. This remains a topic of further research that could have implications on treatment of CVID.…”

“…The effect of HIV infection on patients with CVID is not completely understood; however, in rare cases, CVID has been reported to resolve transiently or permanently in patients with HIV infection. [22][23][24][25][26] This resolution is based on the stimulation and recovery of IgG and IgM production following HIV infection in patients with CVID. Notably, IgA levels remained undetectable in these cases-a finding consistent with the concept that specific immunoregulatory and possibly environmental factors are required to induce CVID in patients with select IgA deficiency.…”