American Indians Have a Higher Risk of Sjögren's Syndrome and More Disease Activity Than European Americans and African Americans

Scofield, R. Hal; Sharma, Rohan; Pezant, Nathan; Kelly, Jennifer A.; Radfar, Lida; Lewis, David M.; Kaufman, C. Erick; Cioli, S; Harris, Judy; Grundahl, Kiely; Rhodus, Nelson L.; Wallace, Daniel J.; Weisman, Michael H.; Venuturupalli, Swamy; Brennan, Michael T.; Koelsch, Kristi A.; Lessard, Christopher J.; Montgomery, Courtney; Sivils, Kathy L.; Rasmussen, Astrid

doi:10.1002/acr.24003

Cited by 8 publications

(17 citation statements)

References 36 publications

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“…Conversely, the patients included in our analysis were more ethnically diverse ( Table 1 ). Hence, it is tempting to speculate that the increased number of DEGs observed in our data set is a direct reflection of ethnic diversity and more representative of the genetic heterogeneity commonly associated with this disease ( 86 , 87 ). It is also plausible that the differences in focus scores between the two patient groups may in part account for the significant difference in DEGs.…”

Section: Discussionmentioning

confidence: 95%

Transcriptomic and Network Analysis of Minor Salivary Glands of Patients With Primary Sjögren’s Syndrome

et al. 2021

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Primary Sjögren’s syndrome (pSS) is a systemic autoimmune disease characterized primarily by immune-mediated destruction of exocrine tissues, such as those of the salivary and lacrimal glands, resulting in the loss of saliva and tear production, respectively. This disease predominantly affects middle-aged women, often in an insidious manner with the accumulation of subtle changes in glandular function occurring over many years. Patients commonly suffer from pSS symptoms for years before receiving a diagnosis. Currently, there is no effective cure for pSS and treatment options and targeted therapy approaches are limited due to a lack of our overall understanding of the disease etiology and its underlying pathology. To better elucidate the underlying molecular nature of this disease, we have performed RNA-sequencing to generate a comprehensive global gene expression profile of minor salivary glands from an ethnically diverse cohort of patients with pSS. Gene expression analysis has identified a number of pathways and networks that are relevant in pSS pathogenesis. Moreover, our detailed integrative analysis has revealed a primary Sjögren’s syndrome molecular signature that may represent important players acting as potential drivers of this disease. Finally, we have established that the global transcriptomic changes in pSS are likely to be attributed not only to various immune cell types within the salivary gland but also epithelial cells which are likely playing a contributing role. Overall, our comprehensive studies provide a database-enriched framework and resource for the identification and examination of key pathways, mediators, and new biomarkers important in the pathogenesis of this disease with the long-term goals of facilitating earlier diagnosis of pSS and to mitigate or abrogate the progression of this debilitating disease.

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Section: Discussionmentioning

confidence: 95%

Transcriptomic and Network Analysis of Minor Salivary Glands of Patients With Primary Sjögren’s Syndrome

et al. 2021

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“…It will also be useful to study whether differences in socioeconomic status (e.g., residence in urban vs. rural areas) or access to care or latitudinal differences between members of similar tribal groups influence epidemiological characteristics of SS in Africa. 5,8 Moreover, it will be of great interest to assess risk factors across pSS and SS associated with other autoimmune diseases, to contribute to the ongoing debate on the rationale…”

Section: Discussionmentioning

confidence: 99%

“…Notable missing key variables are classification criteria in 16 included studies and the frequency of lymphoma among SS patients. 1,2,8,34 For instance, only 2 of 10 studies addressing pSS and sSS each used the recommended (2002 American-European Consensus Group) classification criteria. 37 However, this limitation more likely led to underestimation of the number of fulfilled classification criteria than decrease of classification reliability in corresponding studies, as we excluded studies focusing on the sicca syndrome.…”

Section: Discussionmentioning

confidence: 99%

Epidemiology of Sjögren Syndrome in Africa

et al. 2022

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Background:The epidemiology of Sjögren syndrome (SS) has been extensively studied in America, Europe, and Asia.Objective: To summarize available data on the epidemiology of SS in Africa. Methods: MEDLINE, EMBASE, and African Journals Online were searched from inception up to May 17, 2020, to identify relevant articles. Data gleaned from these reports have been summarized narratively in this review.Results: Twenty-one hospital-based studies were included. These studies reported 744 cases of SS. The mean age at diagnosis varied between 28 and 73.6 years, and the female proportion ranged from 83.3% to 100%. There was no population-based incidence or prevalence. Among people with autoimmune and other rheumatic conditions, the frequency of primary SS was in the range 1.9% to 47.6%, whereas that of rheumatoid arthritisassociated secondary SS was in the range 4.3% to 100%. Sicca symptoms were the commonest features, with most frequently involved organs being joints, lungs, and neurological structures. Main autoantibodies were anti-Ro/SS antigen A, anti-La/SS antigen B, and antinuclear antibodies. Conclusions:The epidemiology of SS is poorly characterized in Africa.Available data are broadly consistent with those from other populations. Extensive and high-quality research is urgently needed.

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“…These potential inflammatory mediators have also not been considered in current drinking-water standards or regulatory risk assessment evaluations (Erdei et al 2019). This developing research on the potential inflammatory triggering processes of uranium are platformed on an already higher known risk of some autoimmune (i.e., inflammatory) conditions in AI populations (Peschken et al 2010;Scally et al 2017;Scofield et al 2020).…”

Section: American Indian Considerationsmentioning

confidence: 99%

Uranium Exposure in American Indian Communities: Health, Policy, and the Way Forward

Redvers

Chischilly²,

Warne

et al. 2021

Environ Health Perspect

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Background: Uranium contamination of drinking-water sources on American Indian (AI) reservations in the United States is a largely ignored and underfunded public health crisis. With an estimated 40% of the headwaters in the western U.S. watershed, home to many AI reservation communities, being contaminated with untreated mine waste, the potential health effects have largely been unexplored. With AI populations already facing continued and progressive economic and social marginalization, higher prevalence of chronic disease, and systemic discrimination, associations between various toxicant exposures, including uranium, and various chronic conditions, need further examination. Objectives: Uranium’s health effects, in addition to considerations for uranium drinking-water testing, reporting, and mitigation in reference to AI communities through the lens of water quality, is reviewed. Discussion: A series of environmental health policy recommendations are described with the intent to proactively improve responsiveness to the water quality crisis in AI reservation communities in the United States specific to uranium. There is a serious and immediate need for better coordination of uranium-related drinking-water testing and reporting on reservations in the United States that will better support and guide best practices for uranium mitigation efforts. https://doi.org/10.1289/EHP7537

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American Indians Have a Higher Risk of Sjögren's Syndrome and More Disease Activity Than European Americans and African Americans

Cited by 8 publications

References 36 publications

Transcriptomic and Network Analysis of Minor Salivary Glands of Patients With Primary Sjögren’s Syndrome

Transcriptomic and Network Analysis of Minor Salivary Glands of Patients With Primary Sjögren’s Syndrome

Epidemiology of Sjögren Syndrome in Africa

Uranium Exposure in American Indian Communities: Health, Policy, and the Way Forward

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