Microbial epitopes act as altered peptide ligands to prevent experimental autoimmune encephalomyelitis.

Molecular mimicry refers to structural homologies between a self-protein and a microbial protein. A major epitope of myelin basic protein (MBP), p87-99 (VHFFKNIVTPRTP), induces experimental autoimmune encephalomyelitis (EAE). VHFFK contains the major residues for binding of this self-molecule to T cell receptor (TCR) and to the major histocompatibility complex. Peptides from papilloma virus strains containing the motif VHFFK induce EAE. A peptide from human papilloma virus type 40 (HPV 40) containing VHFFR, and one from HPV 32 containing VHFFH, prevented EAE. A sequence from Bacillus subtilis (RKVVTDFFKNIPQRI) also prevented EAE. T cell lines, producing IL-4 and specific for these microbial peptides, suppressed EAE. Thus, microbial peptides, differing from the core motif of the self-antigen, MBPp87-99, function as altered peptide ligands, and behave as TCR antagonists, in the modulation of autoimmune disease.

Autoimmune diseases prior to the diagnosis of multiple sclerosis: a population-based case-control study.

The objective of this study was to determine whether patients with multiple sclerosis (MS) are more likely to have other autoimmune disorders particularly prior to the diagnosis of MS. We conducted a population-based case-control study of patients enrolled in the Northern California Kaiser Permanente Medical Care Program. Electronic clinical records through 2005 were used to ascertain incident and prevalent MS cases and identify the presence and timing of 44 other diagnoses. Controls were matched 5:1 for gender, age, and Kaiser membership characteristics. We identified 5296 MS cases (including 924 diagnosed between 2001 and 2004) and 26,478 matched controls. Prior to MS diagnosis, cases were more likely than controls to have uveitis (OR = 3.2, 95%; CI 1.7-5.7), inflammatory bowel disease (IBD, OR = 1.7; 95%CI 1.2-2.5), and Bell's palsy (OR = 3.2; 95%CI 1.2-8.3). Cases were also more likely to develop Guillain- Barré syndrome (GBS, OR = 5.0; 95%CI 1.6-15.4) and bullous pemphigoid (OR = 6.7; 95%CI 1.5-29.9). Cases were not more likely than controls to have or to develop rheumatoid arthritis, lupus or thyroiditis. MS may share environmental triggers, genetic susceptibilities and/or alterations in immune homeostasis with IBD and uveitis, but not with other autoimmune disorders.

Obesity, dieting, and multiple sclerosis.

BACKGROUND: Obesity is common in the United States and is associated with a higher risk of relapse and comorbidities, and increased disease progression, in people with MS. METHODS: We examined the prevalence of overweight and obesity in the MS Sunshine Study, a matched case-control study of multiple sclerosis in Southern California (470 cases, 519 controls). We reported the proportion of participants who adopted a specific diet for nutrition or weight loss purposes, and identified independent predictors of dieting. RESULTS: In the total population, 32% and 37% were overweight and obese, respectively. Case participants were no more likely to adopt a specific diet for nutrition or weight loss purposes than control participants (10% and 11%, respectively). Being obese, younger, female or non-Hispanic were independently associated with dieting. CONCLUSION: Despite the evidence that obesity can worsen MS prognosis, and the high prevalence of overweight/obesity, case participants were no more likely to adopt a specific diet than control participants. Improved nutrition education may help people with MS make healthy dietary changes for nutrition or weight loss purposes.

Association between maternal inflammatory bowel disease and adverse perinatal outcomes.

OBJECTIVE: To examine whether inflammatory bowel disease (IBD) is associated with ischemic/inflammatory conditions during pregnancy. STUDY DESIGN: A retrospective cohort study using the 2000 to 2012 Kaiser Permanente Southern California maternally-linked medical records (n=395 781). The two major subtypes of IBD, ulcerative colitis and Crohn's diseases were studied. Adjusted odds ratios (ORs) were used to quantify the associations. RESULT: A pregnancy complicated by IBD was associated with increased incidence of small-for-gestational age birth (OR=1.46, 95% confidence interval (CI)=1.14 to 1.88), spontaneous preterm birth (OR=1.32, 95% CI=1.00 to 1.76) and preterm premature rupture of membranes (OR=1.95, 95% CI=1.26 to 3.02). Further stratifying by IBD subtypes, only ulcerative colitis was significantly associated with increased incidence of ischemic placental disease, spontaneous preterm birth and preterm premature rupture of membranes. CONCLUSION: The findings underscore the potential impact of maternal IBD on adverse perinatal outcomes. Clinicians should be aware that the association between IBD and adverse perinatal outcome varies by IBD subtypes.

Spinal cord lesions and disability in Hispanics with multiple sclerosis.

Longitudinally extensive spinal cord lesions (LESCLs) are believed to occur predominantly with opticospinal multiple sclerosis (OSMS) and are associated with disability. The purpose of this study is to describe the prevalence and patterns of spinal cord lesions in Hispanics with multiple sclerosis (MS) and OSMS and their association with disability. A cross-sectional study of 164 patients with complete MRIs was used. In each case the spinal cord was classified: LESCLs, scattered spinal cord lesions (sSCLs) or no spinal cord lesions (noSCLs). Clinical course was defined as classical MS or OSMS. Risk of disability (Expanded Disability Status Scale ≥4.0) was adjusted for age, disease duration and sex using logistic regression. A total of 125/164 (73 %) MS patients had spinal cord lesions (sSCLs, 57 %; LESCLs, 19 %), but only 11 (7 %) had OSMS. LESCLs were associated with disability (p < 0.0001), longer disease duration (p < 0.0001) and MS (n = 21 vs. n = 10 OSMS; p < 0.0001). LESCLs were also associated with the greatest risk to disability (OR 7.3, 95 % CIs 1.9-26.5; p = 0.003; sSCLs OR 2.5, 95 % CIs 0.9-7.1; p = 0.09) compared with noSCLs. LESCLs are more common than OSMS and are associated with worse disability even in patients with MS. These results suggest that LESCLs are a more important marker of disability in MS than OSMS and may be an early indicator of more aggressive disease in this population.

Incidence of acquired CNS demyelinating syndromes in a multiethnic cohort of children.

OBJECTIVE: To determine whether the incidence and clinical features of pediatric multiple sclerosis (MS) and other forms of pediatric acquired demyelinating syndromes (ADS) vary by race/ethnicity in a population-based cohort. METHODS: We used a combination of electronic database searches followed by complete medical records review to identify all children diagnosed with MS and ADS in the multiethnic membership of Kaiser Permanente Southern California from January 1, 2004, to December 31, 2009. Incidence rates were standardized to the US census by age and gender. RESULTS: We identified 81 incident cases of ADS from 4.87 million person-years of observation in children 0-18 years of age. The incidence rate of pediatric MS was 0.51 per 100,000 person-years (95% confidence interval [CI] 0.33-0.75) and incidence of other forms of ADS including optic neuritis, transverse myelitis, other forms of clinically isolated syndrome (CIS), and acute disseminated encephalomyelitis (ADEM) was 1.56 (95% CI 1.23-1.95) for an overall incidence of ADS of 1.66 per 100,000 person-years (95% CI 1.32-2.06). Incidence of ADS was higher in black (4.4 per 100,000 person-years, 95% CI 2.5-7.2, p < 0.001) and Asian/Pacific Islander (2.8, 95% CI 1.2-5.2, p = 0.02) than white (1.03, 95% CI 0.6-1.7) and Hispanic (1.5, 95% CI 1.1-2.1, per 100,000 person-years) children. Black children were also significantly more likely to have MS than white children (p = 0.001). Children who presented with ADEM were significantly younger than children with other types of ADS clinical presentations (mean age 5.6, range 0.7-17.6 years vs 14.6, range 2.7-18.5, respectively). CONCLUSIONS: The incidence of pediatric acquired demyelinating syndromes is 1.66 per 100,000 person-years in a population-based cohort of Southern Californian children. The incidence of ADS and MS is higher in black children compared with white and Hispanic children.