Background M-phase phosphoprotein (MPP-1), also termed kinesin interacting protein (KIF20B), is a 210 kDa protein that is highly expressed during cell division. Autoantibodies to MPP-1 were first described in approximately 25% of patients with idiopathic ataxia, but recent studies have indicated that they are also found in systemic lupus erythematosus (SLE). The goals of this study were to determine the frequency of anti-MPP-1 in a local SLE cohort and then identify demographic, clinical, and serologic correlations.
Methods Patients fulfilling the American College of Rheumatology (ACR) or Systemic Lupus International Collaborating Clinics (SLICC) Classification Criteria for SLE were enrolled in the SouThern Alberta Registry for Lupus EryThematosus (STARLET) cohort (Calgary, Canada). Demographic, clinical information (disease activity – SLEDAI-2K; damage – SLICC/ACR DI), and sera were collected at time of enrollment. Antibodies to MPP-1 were determined by an addressable laser bead immunoassay (ALBIA) utilizing an in vitro expressed MPP-1 cDNA construct inserted into a GFP vector (Clontech Laboratories Inc., Saint-Germain-en-Laye, France). ALBIA results were expressed as median florescence units (MFU) and a dilution of ≥1:500 MFU was considered highly positive. Univariable analysis was performed to determine associations between the prevalence of high positive anti-MPP-1 and demographic (age, sex, race/ethnicity), clinical features (SLEDAI-2K and SLICC/ACR DI total scores and subscales and neurological subscale of the ACR and SLICC Classification Criteria), medications, other autoantibodies (anti-dsDNA, extractable nuclear antigens, and anti-phospholipid antibodies).
Results One hundred and forty SLE patients were included; 89.3% were female with a mean age of 47.3 years (SD 16.3) and disease duration of 13.9 years (SD 11.6). The prevalence of high titre anti-MPP-1 was 15.0% (21/140) respectively. Univariable analysis demonstrated that high anti-MPP-1 positivity was associated with a higher total SLEDAI-2K score (Odds Ratio (OR), 1.1 [95% CI 1.0 to 1.3]), particularly with the serositis (OR 3.0, [95% CI 1.4 to 6.6]) and immunological subscales (OR 2.0, [95% CI 1.4 to 2.9]). High anti-MPP-1 positivity was also associated with anti-dsDNA (OR 5.5 [95% CI 1.8 to 16.6]), anti-SSA/Ro60 (OR 3.1 [95% CI 1.0 to 8.9]) and anti-phosphotidylserine/prothrombin complex (aPS/PT)-IgG (OR 3.6 [95% CI 1.1 to 11.5]).
Conclusions High titer anti-MPP-1 antibodies were common in this SLE cohort (15.0%) and may be associated with greater clinical and serologic SLE disease activity. A larger study is currently underway to more clearly delineate its role as a biomarker in SLE.
Acknowledgements The authors are grateful for the technical assistance of Ms. Haiyan Hou and Meifeng Zhang (Mitogen Advanced Diagnostics, University of Calgary).
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