A new study has demonstrated high prevalence rates of reduced serum immunoglobulin (Ig) concentrations in patients with multiple sclerosis (MS) with or without disease-modifying treatments. Although the significance of the levels are unknown, researchers believe that the information is useful to monitor IgG levels, especially with anti-B-cell therapies and consider IgG substitution when levels drop below 400 mg/dl.

Primary immunodeficiency is a rare disease, with the most prevalent forms occurring as Ig M and A deficiencies (0.37% and 0.2%, respectfully). It is commonly known that IgG deficiency appears in 1.7% of patients with celiac disease and IgA deficiency occurs in 5.2% of patients with systemic lupus erythematosus. However, the frequency of hypogammaglobulinemia is unknown in patients with MS.

In this study, researchers wanted to evaluate the frequency of reduced Ig concentrations and its association with immunotherapy and disease course in 2 independent cohorts with MS.

The retrospective analysis of 2 independent European cohorts included approximately 327 patients with MS; 226 from Bern University Hospital in Bern, Switzerland and Eginition University Hospital in Athens, Greece. Serum IgG concentrations were frequently under lower limits of normal (LLN) in both MS cohorts, even when considering only untreated patients.

Serum Ig concentrations were analyzed in the respective main laboratories. In the case of multiple Ig measurements, the most recent serum Ig sample was used for the analysis. With reference to treatment status, patients were indexed as having received corticosteroids if administered intravenously less than 4 weeks before blood sampling. All data were acquired during routine clinical practice. The following cut-offs were used to define the LLN of Ig concentrations: IgG < 700 mg/dl, IgM < 40 mg/dl, and IgA < 70 mg/dl.18

According to the study, patients with MS were significantly more likely to have IgG concentrations below LLN and below 600 mg/dl compared with the controls (n=58). Between both patient groups, researchers found no significant difference in frequencies of IgA and IgM concentrations under LLN.

Independent of age, patients with secondary progressive MS had lower IgG concentrations than patients with relapsing-remitting and primary progressive forms of MS. After adjusting for sex, age, and disease course, IgG concentrations were lower in patients treated with rituximab (p = 0.001; n = 42/327), intravenous corticosteroids (p < 0.001; n = 16/327), natalizumab (p < 0.001; n = 48/327), and fingolimod (p = 0.003; n = 6/327).

The study demonstrated that a substantial proportion of patients with MS had serum IgG concentrations below the LLN. The study noted that these levels were influenced by the MS disease course and certain immunotherapies (rituximab, intravenous corticosteroids, natalizumab, and fingolimod).

The study authors note that the information is useful to monitor IgG levels, especially with anti-B-cell therapies and consider IgG substitution when levels drop below 400 mg/dl.

  1. Zoehner G, Miclea A, Salmen A, et al. Reduced serum immunoglobulin G concentrations in multiple sclerosis: prevalence and association with disease-modifying therapy and disease course. Published September 27, 2019. https://journals.sagepub.com/doi/full/10.1177/1756286419878340?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub%3Dpubmed. Accessed October 28, 2019.