Enhanced serum immunoglobulin G clearance in myotonic dystrophy-associated hypogammaglobulinemia: a case series and review of the literature

Abstract

BackgroundMyotonic dystrophy type 1 is an autosomal dominant disorder characterized by muscle weakness, myotonia, cataracts, and cardiac conduction defects; it is associated with expansions of cytosine-thymine-guanine repeats in the myotonic dystrophy protein kinase. Hypogammaglobulinemia is a lesser known association of myotonic dystrophy type 1 and the underlying pathogenesis of immunoglobulin G depletion remains unclear.Case presentationHere we report a kindred of two members (a 62-year-old white woman and a 30-year-old white man; mother and son) with myotonic dystrophy type 1-associated hypogammaglobulinemia associated with altered intravenous immunoglobulin elimination kinetics and reduced half-life. There was no history of systemic immunosuppression or renal or gastrointestinal protein loss in either patient, and no underlying case for a secondary immunodeficiency could be found. One patient required fortnightly intravenous immunoglobulin to maintain adequate trough immunoglobulin G levels.ConclusionsOngoing study of myotonic dystrophy type 1-associated hypogammaglobulinemia using contemporary tools of genomic medicine may help to further delineate the pathogenesis of this entity.

Targeting FcRn for immunomodulation: Benefits, risks, and practical considerations

“…Hypogammaglobulinemia is a lesser-known symptom of myotonic dystrophy type 1, with patients typically having low IgG 1 and IgG 3 , with normal levels of IgM, IgA, IgG 2 , IgG 4 , and albumin; patients retain the ability to produce protective specific vaccine-related antibody titers (Table II). 62 It has previously been proposed that alterations to the FcRn receptor in myotonic dystrophy type 1 lead to impaired recycling and hypercatabolism of IgG. 82 Although patients with myotonic dystrophy type 1 and hypogammaglobulinemia have been reported to experience increased infection risk, the resulting burden of infection in these patients does not appear to correlate directly with serum levels of IgG, and the mechanism by which IgG levels are reduced remains unclear.…”

“…82 Although patients with myotonic dystrophy type 1 and hypogammaglobulinemia have been reported to experience increased infection risk, the resulting burden of infection in these patients does not appear to correlate directly with serum levels of IgG, and the mechanism by which IgG levels are reduced remains unclear. 62 Mannosyl-oligosaccharide glucosidase mutations represent 1 of more than 100 types of congenital disorders of glycosylation identified to date and caused by defects in protein or lipid glycosylation. 63 N-glycosylation disorders such as mannosyloligosaccharide glucosidase-congenital disorders of glycosylation result in intrinsic defects, affecting immunoglobulin structure and stability, and can alter IgG function and half-life (Table II).…”

“…Plasma donation, PLEX, and IA all involve removal of blood components with greater or lesser degrees of selectivity for IgG ( Table II ). 18 , 23 , 24 , 25 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 These procedures result in the reduction of existing antibodies, while leaving production of immunoglobulins by plasma cells intact ( Table II ). Levels of serum proteins, including IgG, are subsequently restored by new production and redistribution from the extracellular space.…”

“… 82 Although patients with myotonic dystrophy type 1 and hypogammaglobulinemia have been reported to experience increased infection risk, the resulting burden of infection in these patients does not appear to correlate directly with serum levels of IgG, and the mechanism by which IgG levels are reduced remains unclear. 62 …”

Role of Immunoglobulins in Muscular Dystrophies and Inflammatory Myopathies

“…The evidence of IVIG usage in DM is limited to hypothesis stage as described in the study of Sasson et al. ( 78 ) where it was documented the clinical history of two DM1 patients (mother and son) with defects in circulating IgG related to kinetics and half-life: no defects in lymphocytes’ population were evidenced by cytofluorimetric FACS analysis nor other laboratory markers such as full blood count, electrolytes and urea were pathologic. Surprisingly, the patient with more significant serum IgG deficit had lower problems of infection.…”