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Amr H Sawalha

Publications and source records attributed to Amr H Sawalha.

7 recordsLinked to original sources
PubMed2024

Genetic Analysis of Asymptomatic Antinuclear Antibody Production.

OBJECTIVE: Antinuclear antibodies (ANA) are detected in up to 14% of the population, and many individuals with ANA are asymptomatic. The literature on the genetic contribution to asymptomatic ANA positivity is limited. In this study, we aimed to perform a genome-wide association study of asymptomatic ANA positivity in multiple populations. METHODS: Asymptomatic individuals who were either ANA positive or ANA negative from the All of Us Research Program were included in this study, selecting those with an ANA test performed by immunofluorescence and no evidence of autoimmune disease. Imputation was performed, and a multipopulation meta-analysis including approximately 6 million single-nucleotide polymorphisms (SNPs) was conducted. Genome-wide SNP-based heritability was estimated using the Genome-wide Complex Trait Analysis&#xa0;software. A cumulative genetic risk score for lupus was constructed using previously reported genome-wide significant loci. RESULTS: A total of 1,955 asymptomatic ANA positive and 3,634 asymptomatic ANA negative individuals across three populations were included. The multipopulation meta-analysis revealed SNPs with a suggestive association (P <1 &#xd7; 10-5) across 8 different loci, but no genome-wide significant loci were identified. A gene variant upstream of HLA-DQB1, (rs17211748, P = 1.4 &#xd7; 10-6, odds ratio 0.82, 95% confidence interval 0.76-0.89), showed the most significant association. The heritability of asymptomatic ANA positivity was estimated to be 24.9%. Individuals who were asymptomatic and ANA positive did not exhibit increased cumulative genetic risk for lupus compared with individuals who were ANA negative. CONCLUSION: ANA production is not associated with significant genetic risk and is primarily determined by environmental factors.

Humans↗
PubMed2004

Antinuclear autoantibodies in systemic lupus erythematosus.

PURPOSE OF REVIEW: The production of autoantibodies against nuclear antigens is the hallmark of systemic lupus erythematosus. Among the large number of autoantibodies known, only a limited number appear to be clinically important. The various autoantibodies have different clinical significance in lupus patients. In this review, we will discuss the various antinuclear autoantibodies detected in lupus patients, their potential pathogenic role, and their usefulness in clinical practice. RECENT FINDINGS: Recent advances include the clear demonstration of autoantibody transport into living cells, a process that clearly includes interactions with a number of cellular components that may play a role in cellular dysfunction and disease. Also, the anti-Sm B/B' response originates from a single antigenic epitope that appears to be the same structure in different patients, before spreading to other epitopes and becoming the typically mature, complex humoral autoimmune anti-Sm autoantibody response. SUMMARY: The existing data strongly support a central role of autoantibodies in the pathogenesis of lupus. Better characterization of autoantibodies, their mechanisms of production, and their interactions with various cellular constituents will clarify the pathogenesis of this disease.

Antibodies, Antinuclear↗
PubMed2004

Association between systemic lupus erythematosus and Helicobacter pylori seronegativity.

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.

Adolescent↗
PubMed2003

The genetics of primary Sjögren's syndrome.

Primary Sjögren's syndrome is an autoimmune disease characterized clinically by dryness of the eyes and mouth. The use of different classification criteria for primary Sjögren's syndrome has led to dramatically different estimates of prevalence and incidence. Despite this, several genetic and environmental factors are thought to play a role in the susceptibility to primary Sjögren's syndrome, as is the current conceptual formulation of the pathogenesis of many other autoimmune maladies. Primary Sjögren's syndrome appears a complicated polygenic disorder with many genes interacting with environmental factors. Similar to many other polygenic autoimmune rheumatic diseases, human leukocyte antigen associations have been reported and confirmed. Additionally, other non-human leukocyte antigen candidate genes have been reported to reveal association with primary Sjögren's syndrome, but, in general, these effects are not confirmed. The authors review the human leukocyte antigen and non-human leukocyte antigen genetic associations herewith, knowing that new technologies are providing access to the entire genome for association studies. No doubt a much more comprehensive description of the genetics of this disorder will soon emerge.

Genetic Predisposition to Disease↗
PubMed2003

Panniculitis: a presenting manifestation of disseminated histoplasmosis in a patient with rheumatoid arthritis.

We report a case of histoplasma panniculitis in a patient with rheumatoid arthritis treated with multiple immunosuppressive agents including infliximab. The patient presented with erythematous plaques involving the right upper anterior abdominal wall, the right flank and later extension to involve the left flank and the left axilla. The histopathologic examination of these lesions was consistent with lobular panniculitis and the cultures of these lesions and blood grew Histoplasma capsulatum. The clinical and histopathologic picture of histoplasma panniculitis and rheumatoid arthritis-associated panniculitis can be very similar, but the treatment is clearly different. Our case emphasizes the importance of considering rare manifestations of opportunistic infections in an era of widespread use of immunosuppressive medications in the field of rheumatology.

Journal Article↗