Plasma cell disorders in HIV-infected patients: epidemiology and molecular mechanisms

Abstract

Highly active antiretroviral therapy (HAART) has significantly improved the outcome and survival of human immunodeficiency virus (HIV)-infected patients. Subsequently, long-term morbidities including cancer have become of major public health and clinical interest for this patient population. Plasma cell disorders occur at higher incidence in HIV-infected patients; however, the molecular mechanisms driving the plasma cell disease process and the optimal management for these patients remain to be defined. This article provides an up-to-date review of the characteristics and management of HIV-infected patients with plasma cell disorders. We first present 3 cases of plasma cell disorders in HIV-infected patients, ranging from polyclonal hypergammaglobulinemia to symptomatic multiple myeloma. We then discuss the epidemiology, clinical presentation, and management of each of these plasma cell disorders, with an emphasis on the molecular events underlying the progression of plasma cell diseases from monoclonal gammopathy to symptomatic multiple myeloma. We propose a three-step hypothesis for the development of multiple myeloma. Finally, we discuss the use of high dose chemotherapy and autologous hematopoietic stem cell transplantation in the treatment of HIV-infected patients with multiple myeloma. Our review includes the care of HIV-infected patients with plasma cell disorders in the current era of HAART and novel agents available for the treatment of multiple myeloma.

Compartmentalized intrathecal immunoglobulin synthesis during HIV infection — A model of chronic CNS inflammation?

“…Serum hypergammaglobulinemia is a common finding during HIV infection and is either monoclonal, oligoclonal or polyclonal (Konstantinopoulos et al, 2007), the oligoclonal pattern being present in the serum of about 50% of patients when sensitive techniques like isoelectrofocusing are used (Laurijssens et al, 1993;del Bono et al, 1998). This synthesis is commonly attributed to HIVinduced non-specific B-cell activation due to T-cell depletion and virus-induced immune hyperactivation, but it mostly has little clinical consequence (Coker et al, 2013). Qualitative data on nonspecific intrathecal synthesis have not yet been extensively examined and could be attributed to synthesis against auto-antigens, opportunistic infectious agents or against a broad non-HIV-related infectious agent.…”

Association of serum albumin and aspartate transaminase with 5-year all-cause mortality in HIV/hepatitis C virus coinfection and HIV monoinfection

“…In HIV-infected individuals, early studies found that higher gamma globulin predicted mortality in persons with pneumocystis pneumonia[6] and it is well recognized that polyclonal hypergammaglobulinemia often accompanies HIV infection[7]. More recently, low serum albumin has been independently associated with increased mortality risk in large studies of HIV-infected veterans[8] and HIV-infected women[9]; however, it is unknown the degree to which HCV-associated liver disease is associated with lower albumin.…”

Concomitant HIV infection in newly diagnosed multiple myeloma patients is hard to recognise and should be tested for routinely in areas of high endemicity

“…[6] Although HIV probably does not play a direct role in the pathogenesis of MM, as it can neither infect B-cells or plasma cells nor drive their malignant transformation, several indirect mechanisms may be involved in the pathogenesis of plasmacell neoplasias in HIV-associated cases. [7] Polyclonal hypergammaglobulinaemia resulting from chronic B-cell stimulation and loss of normal T-cell function, as seen in the setting of HIV infection, could result in an inclination towards the development of MM in genetically predisposed individuals.…”