Selective IgM Deficiency: Evidence, Controversies, and Gaps

Abstract

Selective Immunoglobulin M deficiency (SIgMD) has been recently included in the inborn errors of immunity (IEI) classification by the International Union of Immunological Societies Expert Committee. The understanding of SIgMD is still extremely limited, especially so in cases of SIgMD in the pediatric population. The epidemiology of SIgMD in the pediatric population is still unknown. The pathogenesis of SIgMD remains elusive, and thus far no genetic nor molecular basis has been clearly established as a definitive cause of this primary immunodeficiency. Recurrent respiratory infections represent the main clinical manifestations in children, followed by allergic and autoimmune diseases. No conclusive data on the correct therapeutic management of SIgMD are available. Although, for most SIgMD patients, Ig replacement therapy is not required, it may be recommended for patients with significantly associated antibody deficiency and recurrent or severe infections. Prophylactic antibiotics and the prompt treatment of febrile illness are crucial. There is insufficient evidence on the prognosis of this condition. Therefore, further studies are required to define the disease trajectories and to increase our understanding of the molecular mechanisms underlying SIgMD in order to facilitate a better clinical, immunological, and prognostic characterization of the condition and develop tailored therapeutic management strategies.

Early postoperative infection in patient with IgM deficiency

“…Selective IgM deficiency is a rare immunological disorder characterized by an isolated reduction or absence in IgM levels, with normal IgG and IgA levels. 1 Patients may present with recurrent infections 1 , 2 allergic manifestations and have associated autoimmune conditions. 1 Despite these known associations, the development of early postoperative infections in patients with selective IgM has not been widely reported in the literature.…”

“… 1 Patients may present with recurrent infections 1 , 2 allergic manifestations and have associated autoimmune conditions. 1 Despite these known associations, the development of early postoperative infections in patients with selective IgM has not been widely reported in the literature. We describe below a case of a patient who had an early postoperative infection after excision of a Merkel cell carcinoma.…”

“…Selective IgM deficiency is an uncommon immunological disorder that has been defined as absent or reduced serum IgM levels in the absence of other immunoglobulin deficiencies. 1 Whilst its pathogenesis remains unclear, proposed mechanisms include a deficiency in Thelper cells, increased isotype specific suppressor Tcells and intrinsic Bcell defects. 1 No clear inheritance pattern has been seen with the condition, although it has been associated with 22q11.2 deletion syndrome.…”

“… 1 Whilst its pathogenesis remains unclear, proposed mechanisms include a deficiency in Thelper cells, increased isotype specific suppressor Tcells and intrinsic Bcell defects. 1 No clear inheritance pattern has been seen with the condition, although it has been associated with 22q11.2 deletion syndrome. 1 Patients affected by selective IgM deficiency commonly present with recurrent infections, as well as allergic and autoimmune manifestations.…”

Refractory and Recurrent Skin Manifestations in an Adult With Selective Immunoglobulin M Deficiency

“…The etiology and pathophysiology of sIgMD are still unknown, and the underlying genetic or molecular mechanism has remained elusive. Given that most patients show normal numbers of circulating surface IgMpositive B cells, the pathogenesis of sIgMD cannot be explained simply by defects in IgM [4]. With normal surface IgM expression in B cells, some studies revealed that insufficient synthesis of secreted IgM mRNA caused the inability of B cells to differentiate into IgM-secreting cells [5,6].…”