Author Of 2 Presentations
P0058 - Decrease of peripheral CD19+ IgG+ B-cells with age and immunotherapy in patients with relapsing remitting Multiple sclerosis. (ID 1459)
Abstract
Background
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system. Little is known about the impact of aging, long term immunotherapy and the combination of both on the immune system in MS.
Objectives
Identification of age and treatment dependent peripheral immune cell changes in MS patients that are distinct from people with other neurological conditions or healthy controls.
Methods
We performed flow cytometric immunophenotyping on whole blood samples of 133 patients with relapsing-remitting MS (range: 17-66 years; median: 39). A cohort of 95 patients with other neurological diseases as well as 13 healthy people served as controls (range: 17-85 years; median: 45). The focus was on characterizing subsets of CD3+ T cells and CD19+ B cells. We used 22 different fluorochromes, split into two panels, labelling well-established surface markers. We observed 20 identifiable subsets in the T cell panel and 15 subsets in the B cell panel. Relative abundance of each identified subset in a sample was plotted against patient age. Linear regression was performed to determine age-related trends. Trend lines of MS and control group were then compared and an F-test used to determine whether slopes significantly differed from one another. As this was an exploratory study, we decided to also compare overall mean values for each parameter between MS and control group, irrespective of age, with a T-test.
Results
We observed a significant age-related decrease in eight subsets and increases in two subsets of the MS-patients. Controls showed a significant decrease in nine subsets and an increase in three. When comparing slopes, all but one were not different between MS patients and controls (p < 0.05). Only the relative abundance of CD19+ IgG+ cells decreased significantly with increasing age in MS patients (p = 0.0007), whereas there was no obvious trend in the control group (p = 0.5887), suggesting the change was specific to the MS group. Comparing slopes of these trend lines with an F-test, significant difference was achieved (p = 0.0261). Omitting age as a factor in the comparison of MS and control patients, we found differences in mean abundance of CD19+ CD27- IgD+ cells (p = 0.0014), CD19+ IgG+ cells (p = 0.0455), CD19+ CD27+ cells (p = 0.0152) and central memory CD3+ CD4+ cells (p = 0.0003). A subgroup analysis comparing CD19+ IgG+ cells in therapy naive (n = 22) and treated (n = 103) patients showed lower mean values in the latter (p = 0.0062), although the treated group did not contain patients that were on B-cell depleting therapy.
Conclusions
Our results show an age-dependent decrease of CD19+ IgG+ B lymphocytes in MS patients which is likely explained by previous immunotherapies. The identified CD19+ IgG+ subgroup represents terminally differentiated populations of B cells. Further studies will focus on their relation to clinical phenotypes, disease trajectories and the impact of different immunotherapies on this subset.
P0426 - A systematic assessment of medical diseases and symptoms preceding the first diagnosis of multiple sclerosis (ID 1159)
Abstract
Background
Previous studies reported that patients who were later diagnosed with multiple sclerosis (MS) showed an altered behavior regarding the use of the healthcare system including increased rates of physician and hospital encounters related to neurological, musculoskeletal and genitourinary as well as psychiatric symptoms up to 10 years before first diagnosis.
Objectives
To explore the occurrence of diseases and symptoms in the 5-year period prior to first diagnosis in patients with multiple sclerosis (MS).
Methods
Using ambulatory claims data we systematically assessed differences in the occurrence of diseases and symptoms in the five years prior to first diagnosis in patients with MS (n=10,524) as compared to patients newly diagnosed with two other autoimmune diseases – Crohn’s disease (n=15,943) and psoriasis (n=99,027) - and individuals without any of these diseases (n=73,430).
Results
Forty-three ICD-10 codes were recorded significantly more frequently for patients with MS in the five years before first diagnosis as compared to controls without autoimmune disease. Many of these findings were confirmed in a comparison to the other two control groups. A high proportion of these ICD-10 codes represent symptoms suggestive of a demyelinating event or other neurological diagnoses. Additionally, six psychiatric diagnoses were recorded more frequently for patients with MS as compared to controls. In a sensitivity analysis excluding patients with symptoms suggestive of an MS relapse or any recordings for neurological diseases prior to first diagnosis, none of these associations remained significant. Six ICD-10 codes were significantly and negatively associated with MS, four of which represented infections of the upper respiratory tract. Here, the negative relations with MS were even more pronounced in the sensitivity analysis.
Conclusions
Our analyses suggest that most of the ICD-10 codes recorded more frequently prior to MS diagnosis are related to misdiagnosed demyelinating events and therefore delayed diagnosis. Other ICD-10 codes more frequently recorded for patients with MS - although not in the sensitivity analysis - included psychiatric diagnoses, which is in accordance with previous studies that report psychiatric disorders as frequent comorbidities in patients with MS. The robust negative association of upper respiratory tract infections with MS diagnosis suggests a link between protection from infection and the occurrence of MS.