Contributions
Abstract: P591
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Background: In patients presenting with a first clinical manifestation of multiple sclerosis (MS) or clinically isolated syndrome (CIS), individual disease course is still unpredictable. Cerebral spinal fluid (CSF) examination currently mainly serves diagnostic proposes. Therefore, the main aim of this study was to determine CSF parameters at the time of diagnosis, which are associated with early disease progression determined by cerebral MRI.
Method: CSF and MRI data of 149 CIS and MS patients were analysed retrospectively. 52 patients did not receive immunomodulatory treatment (IMT) during the observation period. Lumbar puncture was performed less than 12 months after first manifestation of MS. Standardized 3T cerebral MRI was performed at baseline MRI (1-3 months after lumbar puncture) and after 12+/- 3 months. Progress on MRI was defined as the appearance of new T2 hyperintense and/or new gadolinium enhancing lesions on follow-up MRI. CSF parameters included intrathecal IgG, IgA and IgM determined according to Reiber"s formula and corresponding immunoglobulin indices. Furthermore, CSF levels of sCD27 were measured by ELISA in 84 of these patients.
Results: Intrathecal production of IgG and IgM but not IgA is associated with earlier disease progression. Patients with intrathecal IgG and IgM production without IMT have a higher risk of developing a new lesion during the first 12 months (IgG OR=10.7 p=0.002; IgM OR=10.3 p=0.046). Furthermore, IgG and IgM indices in untreated patients are higher in those patients who show an MRI progress (IgG p=0.01; IgM p=0.04). Untreated MS patients with disease progression during the first 12 months also have elevated CSF levels of sCD27 compared to patients without MRI progress (p=0.03). We observed a high correlation between sCD27 levels and IgG index (Spearman r=0.82; p< 0.001).
Conclusion: Elevated CSF levels of sCD27, intrathecal IgG and IgM synthesis seem to be predictors of inflammatory disease activity in newly diagnosed CIS and MS patients. The strong correlation between IgG index and sCD27 levels suggests a pathogenetic link between both biomarkers. Further studies in larger cohorts are warranted to confirm this finding and establish a hierarchy for the clinical relevance of the biomarker.
Disclosure:
A. Klein, R. Selter, V. Biberacher, C. Zimmer: nothing to disclose;
A. Berthele: reports grants from Bayer Healthcare, personal fees from Biogen, Merck Serono, Teva, Novartis, and Genzyme, compensations for clinical trials from Biogen, Novartis, Genzyme, Roche, and Alexion Pharmaceuticals;
M. Mühlau: has received research support from Germany ministry for research and education, German Research Foundation, Hertie-Foundation, Merck-Serono, Novartis;
B. Hemmer: has served on scientific advisory boards for Roche, Novartis, Bayer Schering, and Genentech; has received speaker honoraria from Biogen Idec and Roche; and has received research support from Chugai Pharmaceuticals. He holds part of a patent for the detection of antibodies and T cells against KIR4.1 in a subpopulation of MS patients and genetic determinants of neutralizing antibodies to interferon-beta.
Abstract: P591
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Background: In patients presenting with a first clinical manifestation of multiple sclerosis (MS) or clinically isolated syndrome (CIS), individual disease course is still unpredictable. Cerebral spinal fluid (CSF) examination currently mainly serves diagnostic proposes. Therefore, the main aim of this study was to determine CSF parameters at the time of diagnosis, which are associated with early disease progression determined by cerebral MRI.
Method: CSF and MRI data of 149 CIS and MS patients were analysed retrospectively. 52 patients did not receive immunomodulatory treatment (IMT) during the observation period. Lumbar puncture was performed less than 12 months after first manifestation of MS. Standardized 3T cerebral MRI was performed at baseline MRI (1-3 months after lumbar puncture) and after 12+/- 3 months. Progress on MRI was defined as the appearance of new T2 hyperintense and/or new gadolinium enhancing lesions on follow-up MRI. CSF parameters included intrathecal IgG, IgA and IgM determined according to Reiber"s formula and corresponding immunoglobulin indices. Furthermore, CSF levels of sCD27 were measured by ELISA in 84 of these patients.
Results: Intrathecal production of IgG and IgM but not IgA is associated with earlier disease progression. Patients with intrathecal IgG and IgM production without IMT have a higher risk of developing a new lesion during the first 12 months (IgG OR=10.7 p=0.002; IgM OR=10.3 p=0.046). Furthermore, IgG and IgM indices in untreated patients are higher in those patients who show an MRI progress (IgG p=0.01; IgM p=0.04). Untreated MS patients with disease progression during the first 12 months also have elevated CSF levels of sCD27 compared to patients without MRI progress (p=0.03). We observed a high correlation between sCD27 levels and IgG index (Spearman r=0.82; p< 0.001).
Conclusion: Elevated CSF levels of sCD27, intrathecal IgG and IgM synthesis seem to be predictors of inflammatory disease activity in newly diagnosed CIS and MS patients. The strong correlation between IgG index and sCD27 levels suggests a pathogenetic link between both biomarkers. Further studies in larger cohorts are warranted to confirm this finding and establish a hierarchy for the clinical relevance of the biomarker.
Disclosure:
A. Klein, R. Selter, V. Biberacher, C. Zimmer: nothing to disclose;
A. Berthele: reports grants from Bayer Healthcare, personal fees from Biogen, Merck Serono, Teva, Novartis, and Genzyme, compensations for clinical trials from Biogen, Novartis, Genzyme, Roche, and Alexion Pharmaceuticals;
M. Mühlau: has received research support from Germany ministry for research and education, German Research Foundation, Hertie-Foundation, Merck-Serono, Novartis;
B. Hemmer: has served on scientific advisory boards for Roche, Novartis, Bayer Schering, and Genentech; has received speaker honoraria from Biogen Idec and Roche; and has received research support from Chugai Pharmaceuticals. He holds part of a patent for the detection of antibodies and T cells against KIR4.1 in a subpopulation of MS patients and genetic determinants of neutralizing antibodies to interferon-beta.