H. pylori Infection as a Protective Factor Against MS Risk
H. pylori Infection as a Protective Factor Against MS Risk
Demographic and clinical data of patients with MS and healthy controls is presented in Table 1.
The rate of H. pylori seropositivity in the 299 matched cases was marginally lower than among the controls (p=0.056 unadjusted, p=0.045 adjusted for gender). However, the differences in H. pylori seropositivity pertained almost exclusively to the females (p=0.03), while there was no significant difference in cases versus controls for the males (p=1.0; figure 1A). Comparison of the rates of seropositivity between the matched and non-matched cases did not find any significant differences after adjusting for gender (p=0.2), nor was there any difference in the male/female ratio between matched and unmatched cases (p=0.2). The sampling design did not allow disentanglement of the effects of age of sampling and year of birth, and there was little overlap in birth years for the non-matched cases and the controls. To increase numbers in the comparisons we therefore also created strata based on 2-year age-at-sampling intervals using all the data and carried out case–control analyses using conditional logistic regression, including only those strata in which cases and controls were both represented. In these analyses, cases had a significantly lower seropositivity rate after adjusting for gender (p=0.005), with the effect again notable among the females (p=0.002) and not males (p=0.79; figure 1B).
(Enlarge Image)
Figure 1.
Frequency of Helicobacter pylori seropositivity in patients with multiple sclerosis and healthy controls. (A) H. pylori seropositivity rate was significantly lower in cases than in healthy controls (p=0.045) when matched by year of birth. The difference was significant in females (p=0.03) but not in males (p=1.0). (B) H. pylori seropositivity was overall significantly lower in cases (p=0.005) than in controls when matched by age at sample collection. The effect was significant among females (p=0.002) but not males (p=0.79). *p Values based on matched groups and adjusted for gender in the overall comparison.
When adjusted for age at onset and year of birth there was a significant interaction effect of gender and H. pylori seropositivity on the scaled EDSS/sqrt (Disease Duration) values (p=0.003). There was only marginal evidence of difference between the female and male seronegative cases (p=0.066). However, the female seropositive cases were lower than the corresponding female seronegative cases (p=0.049) while the male seropositive cases were higher than the male seronegative cases (p=0.025), figure 2. There was no significant association between H. pylori seropositivity and relapse rate after adjustment overall (p=0.61) for females (p=0.63) or for males (p=0.99).
(Enlarge Image)
Figure 2.
Association of Helicobacter pylori seropositivity and EDSS score/sqrt (Disease Duration). On adjustment for age and year of birth, EDSS score/sqrt (Disease Duration) significantly interacted with gender and H. pylori seropositivity (p=0.003). The effect was present in females in whom seropositivity was significantly higher than seronegativity (p=0.049), and males in whom seropositivity was significantly lower than seronegativity (p=0.025; EDSS, Extended Disability Status Scale; F-sero-neg, female seronegative; F-sero-pos, female seropositive; M-sero-neg, male seronegative; M-sero-pos, male seropositive; sqrt, square root).
Rates of H. pylori seropositivity were assessed among cases for association with age at sample collection, age at onset, year of birth, gender and primary progressive (PP) status using all the case data. After adjustment for the other variables, there was a significant interaction between gender and PP status (p=0.037), with a significant increase in seroprevalence rates for PP cases compared with non-PP cases among females (p=0.026), but not among males (p=0.88; figure 3).
(Enlarge Image)
Figure 3.
Frequency of Helicobacter pylori seropositivity in primary progressive (PP) and not PP multiple sclerosis cases. Rates of H. pylori seropositivity were assessed among cases for association with age at sample collection, age at onset, year of birth, gender and PP status using all the case data. After adjustment for the other variables H. pylori seropositivity was associated with PP disease course overall (p=0.082). When broken down by gender the effect was significant among females (p=0.026), but not among males (p=0.88).
Overall, there was no significant association among MS cases of carriage of DRB1*1501 and seroprevalence rate (p=0.16). However, within the males there was a significant association (p=0.028), with DRB1*1501 males having higher seroprevalence (figure 4).
(Enlarge Image)
Figure 4.
Association between Helicobacter pylori seropositivity and a carriage of DRB1*1501. Significant association between DRB1*1501 carriage rate and H. pylori seroprevalence was seen in males only (p=0.028), but not the group as a whole (p=0.16). *p Values exact.
Results
Frequency of H. Pylori Seropositivity in Patients With MS and Healthy Controls
Demographic and clinical data of patients with MS and healthy controls is presented in Table 1.
The rate of H. pylori seropositivity in the 299 matched cases was marginally lower than among the controls (p=0.056 unadjusted, p=0.045 adjusted for gender). However, the differences in H. pylori seropositivity pertained almost exclusively to the females (p=0.03), while there was no significant difference in cases versus controls for the males (p=1.0; figure 1A). Comparison of the rates of seropositivity between the matched and non-matched cases did not find any significant differences after adjusting for gender (p=0.2), nor was there any difference in the male/female ratio between matched and unmatched cases (p=0.2). The sampling design did not allow disentanglement of the effects of age of sampling and year of birth, and there was little overlap in birth years for the non-matched cases and the controls. To increase numbers in the comparisons we therefore also created strata based on 2-year age-at-sampling intervals using all the data and carried out case–control analyses using conditional logistic regression, including only those strata in which cases and controls were both represented. In these analyses, cases had a significantly lower seropositivity rate after adjusting for gender (p=0.005), with the effect again notable among the females (p=0.002) and not males (p=0.79; figure 1B).
(Enlarge Image)
Figure 1.
Frequency of Helicobacter pylori seropositivity in patients with multiple sclerosis and healthy controls. (A) H. pylori seropositivity rate was significantly lower in cases than in healthy controls (p=0.045) when matched by year of birth. The difference was significant in females (p=0.03) but not in males (p=1.0). (B) H. pylori seropositivity was overall significantly lower in cases (p=0.005) than in controls when matched by age at sample collection. The effect was significant among females (p=0.002) but not males (p=0.79). *p Values based on matched groups and adjusted for gender in the overall comparison.
Association of H. Pylori Seropositivity With EDSS and Relapse Rate
When adjusted for age at onset and year of birth there was a significant interaction effect of gender and H. pylori seropositivity on the scaled EDSS/sqrt (Disease Duration) values (p=0.003). There was only marginal evidence of difference between the female and male seronegative cases (p=0.066). However, the female seropositive cases were lower than the corresponding female seronegative cases (p=0.049) while the male seropositive cases were higher than the male seronegative cases (p=0.025), figure 2. There was no significant association between H. pylori seropositivity and relapse rate after adjustment overall (p=0.61) for females (p=0.63) or for males (p=0.99).
(Enlarge Image)
Figure 2.
Association of Helicobacter pylori seropositivity and EDSS score/sqrt (Disease Duration). On adjustment for age and year of birth, EDSS score/sqrt (Disease Duration) significantly interacted with gender and H. pylori seropositivity (p=0.003). The effect was present in females in whom seropositivity was significantly higher than seronegativity (p=0.049), and males in whom seropositivity was significantly lower than seronegativity (p=0.025; EDSS, Extended Disability Status Scale; F-sero-neg, female seronegative; F-sero-pos, female seropositive; M-sero-neg, male seronegative; M-sero-pos, male seropositive; sqrt, square root).
The rate of H. Pylori Seropositivity is Related to the Primary Progressive Course of MS for Females
Rates of H. pylori seropositivity were assessed among cases for association with age at sample collection, age at onset, year of birth, gender and primary progressive (PP) status using all the case data. After adjustment for the other variables, there was a significant interaction between gender and PP status (p=0.037), with a significant increase in seroprevalence rates for PP cases compared with non-PP cases among females (p=0.026), but not among males (p=0.88; figure 3).
(Enlarge Image)
Figure 3.
Frequency of Helicobacter pylori seropositivity in primary progressive (PP) and not PP multiple sclerosis cases. Rates of H. pylori seropositivity were assessed among cases for association with age at sample collection, age at onset, year of birth, gender and PP status using all the case data. After adjustment for the other variables H. pylori seropositivity was associated with PP disease course overall (p=0.082). When broken down by gender the effect was significant among females (p=0.026), but not among males (p=0.88).
Overall, there was no significant association among MS cases of carriage of DRB1*1501 and seroprevalence rate (p=0.16). However, within the males there was a significant association (p=0.028), with DRB1*1501 males having higher seroprevalence (figure 4).
(Enlarge Image)
Figure 4.
Association between Helicobacter pylori seropositivity and a carriage of DRB1*1501. Significant association between DRB1*1501 carriage rate and H. pylori seroprevalence was seen in males only (p=0.028), but not the group as a whole (p=0.16). *p Values exact.