Impact of pregnancy-related heart failure on humoral immunity: Clinical relevance of G3-subclass immunoglobulins in peripartum cardiomyopathy

Background The impact and clinical relevance of pregnancy-related heart failure (HF) on humoral immunity are not known. Heart failure is often characterized by immunoglobulins (Ig) that differ in subclass profile with etiology. Subclass immunoglobulins differ in the biologic information they confer in disease. Therefore, given that progressive gestation is associated with immunologic incompetence, we sought to study the relative impact of pregnancy-related onset of HF on humoral immunity. Methods Immunoglobulins (class G and subclasses G1, G2, G3) against cardiac myosin were evaluated in 47 patients with peripartum cardiomyopathy (PPCM) from different global regions: South Africa (n = 15), Mozambique (n = 9), and Haiti (n = 23) and compared with healthy mothers and patients with idiopathic dilated cardiomyopathy (DCM). C-reactive protein, tumor necrosis factor-α, and Fas–Apo-1 were also studied in PPCMs. Results All PPCM groups were similar in Ig profiles. The immunoglobulins, frequencies and reactivities, were markedly and nonselectively raised in PPCM patients compared with DCM. Immunoglobulin frequencies in PPCMs, Haiti: G1 58%, G2 66%, G3 54%; Mozambique: G1 77%, G2 66%, G3 66%; and South Africa: G1 47%, G2 53%, G3 53%, were higher compared with DCMs from South Africa (n = 24): G1 8%, G2 8%, G3 21%, or the United Kingdom (n = 68): G1 10%, G2 8.8%, G3 22% (P < .0001). Hence, unlike the selective up-regulation of immunoglobulins of the G3 subclass (IgG3s) in DCM, class G and all subclass immunoglobulins were raised in PPCM. Of the serological variables, IgG3s (immunoglobulins with proinflammatory characteristics) discriminated NYHA functional status at diagnosis. IgG3-positive patients were in a higher NYHA class at initial presentation (P < .05). Conclusions Immunoglobulin subclass profiles in patients with HF differ with etiology. Unlike DCM, the impact of pregnancy-related HF on humoral immunity is not subclass-restricted. However, raised levels of IgG3s may be of prognostic value in clinical PPCM.