FROM EUROPEAN JOURNAL OF NEUROLOGY
The recently identified autoantibody target in multiple sclerosis, sperm-associated antigen 16 (SPAG16), occurred most often in patients with primary progressive disease and was associated with faster-progressing disease in a case-control cohort study of Belgian and Spanish patients.
Anti-SPAG16 antibody reactivity to the autoantigen, which occurred in 22% of 374 multiple sclerosis (MS) patients overall in the study, was highest among patients with primary progressive MS (PPMS, 34% of 61), followed by secondary progressive MS (SPMS, 26% of 39) and relapsing-remitting MS (RRMS, 19% of 274). Patients with PPMS also had the highest anti-SPAG16 antibody levels, and seropositive PPMS patients had greater worsening of disease over time, judging from a significantly increased progression index relative to seronegative PPMS patients, Laura de Bock of Hasselt University, Diepenbeek, Belgium, and her colleagues reported ( Eur J Neurol. 2015 Dec 26. doi: 10.1111/ene.12925 ).
Anti-SPAG16 antibody seropositivity had a 93% specificity for MS. A total of 7 out of 106 healthy controls were seropositive, based on a cutoff of 70 arbitrary units (AU) for seropositivity using enzyme-linked immunosorbent assay testing. While the mean anti-SPAG16 antibody levels were 58.7 AU in MS patients overall and 16.6 AU in healthy controls, PPMS patients had significantly higher mean levels than did RRMS patients (77.9 vs. 53.2 AU). However, anti-SPAG16 antibody levels in SPMS patients (67.5 AU) did not differ significantly from the other MS groups. The investigators suggested that the “increase in anti-SPAG16 antibody levels [in PPMS patients] is probably due to the significantly increased proportion of PPMS patients (34%) positive for anti-SPAG16 antibodies compared to RRMS patients (19%)” and that anti-SPAG16 antibody seropositivity overall “is possibly linked to disease stage and pathological subtype.”
Age did not correlate with antibody levels, although PPMS patients were significantly younger than their seronegative counterparts when antibodies were detected (48.4 years vs. 56.0 years), compared with patients with other MS subtypes. The seropositive PPMS patients also had significantly shorter mean disease duration than did seronegative PPMS patients (4.6 years vs. 7.9 years) despite having a similar mean Expanded Disability Status Scale (EDSS) score (4.2 vs. 4.1). This indication of a faster disease progression in seropositive PPMS patients was confirmed by their higher mean progression index, compared with seronegative patients (2.7 vs. 1.0); progression index was also significantly correlated with mean score on the MS severity scale (MSSS). Independent predictors of anti-SPAG16 antibody seropositivity on a logistic regression analysis included female sex (odds ratio, 3.91) and progression index (OR, 1.78).
In the overall cohort of MS patients, seropositivity was associated with a significantly higher mean EDSS score than was seronegative status (2.9 vs. 2.5, respectively), although EDSS did not differ according to serologic status in RRMS and SPMS subtypes. Serologic status in those subtypes also was not influenced by sex, disease duration, progression index, or MSSS score.
“Future follow-up of seropositive and seronegative PPMS patients is essential to conclude whether the presence of anti-SPAG16 antibodies could be a novel prognostic biomarker in PPMS. It would be interesting to investigate anti-SPAG16 antibodies in relation to neurofilament light levels, which have been shown to be higher in PPMS and can be used as a prognostic marker, and to investigate whether anti-SPAG16 antibodies can be used as a biomarker for possible treatment monitoring in PPMS,” the investigators wrote.
SPAG16 is known to be upregulated in astrocytes in MS lesions, the researchers noted. “Interestingly, astrocytes are becoming increasingly recognized as important players in MS progression and targets of autoantibodies in MS. It is possible that anti-SPAG16 antibodies are formed due to cell damage and death of astrocytes which leads to the exposure of intracellular antigens such as SPAG16 (epitope spreading).”
The study received support from the Transnationale Universiteit Limburg, Hasselt University, the Flanders Fund for Scientific Research, the Charcot Foundation (Belgium), and Rotary International. Two authors declared financial relationships with companies marketing MS drugs.
