Validation of kappa free light chains as a diagnostic biomarker in multiple sclerosis and clinically isolated syndrome: A multicenter study.

BACKGROUND: Kappa free light chains (KFLCs) have been proposed as a diagnostic biomarker in patients with clinically isolated syndrome (CIS) and multiple sclerosis (MS). OBJECTIVE: The objective of this paper is to validate the diagnostic accuracy of intrathecal KFLC synthesis in a multicenter study. METHODS: KFLCs were measured by nephelometry under blinded conditions in cerebrospinal fluid (CSF) and serum sample pairs of patients with CIS (n = 60), MS (n = 60) and other neurological diseases (n = 60) from four different MS centers. The upper normal limit for intrathecal KFLC concentrations depending on blood-CSF barrier function was previously calculated in a cohort of 420 control patients. RESULTS: Diagnostic sensitivity of intrathecal KFLC synthesis, IgG synthesis according to Reiber, IgG index and oligoclonal bands (OCBs) was 95%, 72%, 73% and 93% in patients with MS and 82%, 47%, 43% and 72% in patients with CIS. Specificity of intrathecal KFLC synthesis was 95% and 98% for all other measures. CONCLUSION: These findings further support the diagnostic value of intrathecal KFLC synthesis in CIS and MS patients and demonstrate a valid, easier and rater-independent alternative to OCB detection.

Kappa free light chains: diagnostic and prognostic relevance in MS and CIS.

BACKGROUND: Quantification of kappa free light chains (KFLC) in cerebrospinal fluid shows high diagnostic sensitivity in multiple sclerosis and clinically isolated syndrome patients. However, a clearly defined threshold value is still missing and a possible prognostic value of the KFLC levels in these patients remains undefined. METHODS: Results of KFLC quantification in 420 controls were used to set an upper limit of normal KFLC concentration in CSF under different blood-CSF-barrier conditions. Additionally, KFLC values of MS and CIS patients were assessed and results were evaluated with reference to the patients corresponding disease courses. RESULTS: The calculated upper limit of normal KFLC-concentration covers 98% of these control patients. Using this cut-off, plasma cell activity in CSF can be detected in 97% of MS patients and in 97% of CIS patients. However, there is no evidence that the extent of KFLC elevation provides prognostic value in MS and CIS patients in this study. CONCLUSION: KFLC determination should become a first line screen in the diagnostic algorithms of MS and CIS. The extent of elevation of intrathecal KFLC has no prognostic value on the disease course in MS and CIS patients.

Serologic markers of autoimmunity in women with polycystic ovary syndrome.

OBJECTIVE: To evaluate whether women with the polycystic ovary syndrome (PCOS) have an increased rate of elevated serum levels of common autoimmunologic parameters. DESIGN: Prospective case-control study. SETTING: Academic research institution. PATIENT(S): One hundred nine women with PCOS and 109 age-matched healthy controls. INTERVENTION(S): Peripheral venous puncture, ultrasonography, questionnaire. MAIN OUTCOME MEASURE(S): Serum levels of antinuclear antibodies (ANAs) were measured by immunometric enzyme immunoassay, serum levels of IgG class autoantibodies against histone, IgG class autoantibodies against nucleosomes, and IgG class autoantibodies against double-stranded (ds) DNA were measured by enzyme immunoassays. RESULT(S): Women with PCOS had significantly elevated serum levels of antihistone and anti-dsDNA antibodies, whereas serum levels of ANAs and antinucleosome antibodies were similar between the two groups. When serum levels of ANAs, antihistone, antinucleosomes, and anti-dsDNA antibodies were correlated with clinical and biochemical parameters, a significant correlation between serum levels of ANAs and serum TSH was established. CONCLUSION(S): Our study shows that serologic parameters of autoimmunity (i.e., antihistone and anti-dsDNA antibodies) are elevated in women with PCOS. A role of autoimmunologic processes in PCOS can be suspected.