Serum antibodies to phosphatidylcholine in MS

Abstract

ObjectiveTo evaluate the value of serum immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies reactive with phosphatidylcholine (PC) and lactosylceramide (LC) as biomarkers in MS.MethodsWe developed an ultrasensitive ELISA technique to analyze serum IgG and IgM antibodies to LC and PC, which we used to analyze samples from 362 patients with MS, 10 patients with non-MS myelin diseases (Non-MSMYDs), 11 patients with nonmyelin neurologic diseases (Non-MYNDs), and 80 controls. MS serum samples included clinically isolated syndrome (CIS, n = 17), relapsing-remitting MS (RRMS, n = 62), secondary progressive MS (SPMS, n = 50), primary progressive MS (PPMS, n = 37), and benign MS (BENMS, n = 36).ResultsWe detected higher levels of serum IgM antibodies to PC (IgM-PC) in MS than control samples; patients with CIS and RRMS showed higher IgM-PC levels than patients with SPMS, PPMS, and BENMS and controls. MS and control samples did not differ in serum levels of IgM antibodies reactive with LC, nor in IgG antibodies reactive with LC or PC.ConclusionsSerum IgM-PC antibodies are elevated in patients with MS, particularly during the CIS and RRMS phases of the disease. Thus, serum IgM-PC is a candidate biomarker for early inflammatory stages of MS.Classification of evidenceThis study provides Class III evidence that serum antibodies to PC are elevated in patients with MS. The study is rated Class III because of the case control design and the risk of spectrum bias: antibody levels in patients with MS were compared with healthy controls.

Role of sphingolipid metabolism in neurodegeneration

“…In addition, antibodies to sphingolipids are detected in SPMS patients and correlate with markers of disease progression such as brain atrophy, a feature of MS thought to be driven by astrocytes and microglia (Bakshi et al., 2016; Farez et al., 2009; Kanter et al., 2006). Interestingly, antibodies to sphingolipids and antibodies to other lipids are independently regulated in MS patients (Sadaba et al In press). Most importantly, sphingolipid metabolism and its products promote inflammation through multiple mechanisms (Maceyka & Spiegel, 2014).…”

IgM to phosphatidylcholine in multiple sclerosis patients: from the diagnosis to the treatment

“…Nevertheless, the incidence of the antibodies to this lipids is lower compared with that of the OIgGBs, 14,17,18,77 and these techniques are not currently used in the diagnosis of MS. 73…”

The Forgotten Brother: The Innate-like B1 Cell in Multiple Sclerosis

“…Furthermore, very recently, in a large cohort study, Sádaba and colleagues examined anti-PtC IgM levels in peripheral blood of MS patients and reported these aAbs were intensely increased during CIS and RRMS. The authors suggested that serum PtC IgMs could be a candidate biomarker for the early inflammatory stages of MS [11]. Nonetheless, one should realize that anti-PtC IgMs are also present in healthy humans' serum, but they do not ligate non-oxidized forms of PtC.…”

“…The mounting recognition that MS pathophysiology is related to neuroinflammatory processes has nourished translational and clinical research lines in the field and yielded important discoveries. For example, (1) at the translational level-the presence of autoantibodies (aAbs) against myelin or damaged neuronal derivates (compromised self-antigens; neoantigens)-was confirmed in the blood plasma and the cerebral spinal fluid (CSF) of MS patients [10,11]. Indeed, a fluctuation in these aAb levels is considered a potential biomarker for the diagnosis of MS [12,13].…”