Serum levels of IgM to phosphatidylcholine predict the response of multiple sclerosis patients to natalizumab or IFN-ß.

We developed an ELISA assay demonstrating the high prevalence of serum IgM to phosphatidylcholine (IgM-PC) in the first stages of multiple sclerosis (MS). We aimed to analyze the role of serum IgM-PC as a biomarker of response to treatment. Paired serum samples from 95 MS patients were obtained before (b.t) and after (a.t) treatment with disease modifying therapies. Patients were classified as non-responders or responders to treatment, according to classical criteria. Serum IgM-PC concentration was analyzed using our house ELISA assay. The level of serum IgM-PC b.t was higher in patients treated later with natalizumab than in those treated with Copaxone (p = 0.011) or interferon-ß (p = 0.009). Responders to natalizumab showed higher concentration of serum IgM-PC b.t than those who did not respond to it (p = 0.019). The 73.3% of patients with the highest level of serum IgM-PC b.t responded to natalizumab. IgM-PC level decreased a.t in both cases, non-responders and responders to natalizumab. IgM-PC levels a.t did not decrease in non-responders to interferon-ß, but in responders to it the IgM-PC level decreased (p = 0.007). Serum IgM-PC could be a biomarker of response to natalizumab or interferon-ß treatment. Further studies would be necessary to validate these results.

Serum antibodies to phosphatidylcholine in MS.

OBJECTIVE: To evaluate the value of serum immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies reactive with phosphatidylcholine (PC) and lactosylceramide (LC) as biomarkers in MS. METHODS: We 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). RESULTS: We 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. CONCLUSIONS: Serum 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 EVIDENCE: This 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.

Mechanisms Underlying Testicular Damage and Dysfunction in Mice With Partial IGF-1 Deficiency and the Effectiveness of IGF-1 Replacement Therapy.

OBJECTIVE: To determine whether insulin-like growth factor (IGF-1) deficiency can cause testicular damage and to examine changes of the testicular morphology and testicular function-related gene expression caused by IGF-1 deficiency. Therefore, this study aims to determine the benefits of low doses of IGF-1 and to explore the mechanisms underlying the IGF-1 replacement therapy. MATERIALS AND METHODS: A murine model of IGF-1 deficiency was used to avoid any factor that could contribute to testicular damage. Testicular weight, score of histopathological damage, and gene expressions were studied in 3 experimental groups of mice: controls (wild-type Igf1(+/+)), heterozygous Igf1(+/-) with partial IGF-1 deficiency, and heterozygous Igf1(+/-) treated with IGF-1. RESULTS: Results show that the partial IGF-1 deficiency induced testicular damage and altered expression of genes involved in IGF-1 and growth hormone signaling and regulation, testicular hormonal function, extracellular matrix establishment and its regulation, angiogenesis, fibrogenesis, inflammation, and cytoprotection. In addition, proteins involved in tight junction expression were found to be reduced. However, low doses of IGF-1 restored the testicular damage and most of these parameters. CONCLUSION: IGF-1 deficiency caused the damage of the blood-testis barrier and testicular structure and induced the abnormal testicular function-related gene expressions. However, low doses of IGF-1 constitute an effective replacement therapy that restores the described testicular damage. Data herein show that (1) cytoprotective activities of IGF-1 seem to be mediated by heat shock proteins and that (2) connective tissue growth factor could play a relevant role together with IGF-1 in the extracellular matrix establishment.