Association Between Systemic Lupus Erythematosus and Helicobacter pylori Seronegativity

AMR H. SAWALHA, WENDI R. SCHMID, STEVEN R. BINDER, DEBRA K. BACINO, and JOHN B. HARLEY

ABSTRACT.

Objective. Helicobacter pylori is a gram negative spiral bacterium that is clearly associated with a variety of gastrointestinal pathologies. A number of non-gastrointestinal diseases have also been associated with H. pylori. We investigated the prevalence of H. pylori seropositivity as part of a larger serologic survey in a group of 466 patients with systemic lupus erythematosus (SLE) and 466 controls.

Methods. We studied subjects for seropositivity against 5 antigens including mumps, measles, rubella, varicella zoster, and H. pylori. The 466 SLE patients were taken from a total of 290 pedigrees multiplex for SLE and matched to 466 controls for age (± 3 yrs), sex, and ethnicity to non-SLE affected individuals, taken mostly from the same collection of pedigrees multiplex for SLE. Assays for seropositivity were performed using a heterogeneous immunoassay technique. Pearson's chi-square was used to test for association of categorical variables and Student t-test for continuous variables. Logistic regression was used to compute the odds ratio for H. pylori seropositivity in patients and controls.

Results. There was a significant difference only in H. pylori seropositivity between SLE cases and their controls. The results were not altered by intrafamilial correlation. Subset analysis by race and sex showed that the differences between the African-American female patients with SLE and their matched controls were responsible for this association. Female African-American patients with SLE had a lower prevalence of H. pylori seropositivity compared to controls (38.1% vs 60.2%, OR 0.41, p = 0.0009, 95% CI 0.24–0.69). Of the 113 African-American female SLE patients in the study group, 43 were seropositive for H. pylori. The mean age of onset for SLE was older in the seropositive group (34.4 yrs) compared to the seronegative SLE patients (28.0 yrs) (t = 2.11, p = 0.039).

Conclusion. Of 5 serologic tests performed, only the frequency of H. pylori seropositivity was different between SLE cases and their controls, and then only in African-Americans. We found an association between being seronegative for H. pylori and the development of SLE in African-American women, who also tend to be younger at the time of disease onset. These findings suggest that there is a possible protective role for H. pylori infection against the development of SLE or that immunoregulatory events leading to H. pylori seropositivity are inversely related to the risk of SLE. (J Rheumatol 2004;31:1546-50)

Key Indexing Terms:

LUPUS
INFECTION
HELICOBACTER PYLORI
SEROLOGY

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From the Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma; Arthritis and Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma; Bio-Rad Laboratories, Hercules, California; and US Department of Veterans Affairs Medical Center, Oklahoma City, Oklahoma, USA.

Supported by National Institutes of Health grants AI42460, AR12253, AI24717, RR15577, AI31584, AR01005, AR048940, AR049084, and the US Department of Veterans Affairs (CC103).

A.H. Sawalha, MD, University of Oklahoma Health Sciences Center; W.R. Schmid; D.K. Bacino, Oklahoma Medical Research Foundation; S.R. Binder, Bio-Rad Laboratories; J.B. Harley, MD, PhD, University of Oklahoma Health Sciences Center, Oklahoma Medical Research Foundation, US Department of Veterans Affairs Medical Center.

Address reprint requests to Dr. J.B. Harley, Oklahoma Medical Research Foundation, 825 NE 13th Street, Oklahoma City, OK 73104. E-mail: john-harley@omrf.ouhsc.edu

Submitted August 1, 2003; revision accepted February 25, 2004.

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