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Featured researches published by David M. Lewis.


Nature Genetics | 2013

Variants at multiple loci implicated in both innate and adaptive immune responses are associated with Sjögren’s syndrome

Christopher J. Lessard; He Li; Indra Adrianto; John A. Ice; Astrid Rasmussen; Kiely Grundahl; Jennifer A. Kelly; Mikhail G. Dozmorov; Corinne Miceli-Richard; Simon Bowman; Susan Lester; Per Eriksson; Maija-Leena Eloranta; Johan G. Brun; Lasse G. Gøransson; Erna Harboe; Joel M. Guthridge; Kenneth M. Kaufman; Marika Kvarnström; Helmi Jazebi; Deborah S. Cunninghame Graham; Martha E. Grandits; Abu N. M. Nazmul-Hossain; Ketan Patel; Adam Adler; Jacen S. Maier-Moore; A. Darise Farris; Michael T. Brennan; James A. Lessard; James Chodosh

Sjögrens syndrome is a common autoimmune disease (affecting ∼0.7% of European Americans) that typically presents as keratoconjunctivitis sicca and xerostomia. Here we report results of a large-scale association study of Sjögrens syndrome. In addition to strong association within the human leukocyte antigen (HLA) region at 6p21 (Pmeta = 7.65 × 10−114), we establish associations with IRF5-TNPO3 (Pmeta = 2.73 × 10−19), STAT4 (Pmeta = 6.80 × 10−15), IL12A (Pmeta = 1.17 × 10−10), FAM167A-BLK (Pmeta = 4.97 × 10−10), DDX6-CXCR5 (Pmeta = 1.10 × 10−8) and TNIP1 (Pmeta = 3.30 × 10−8). We also observed suggestive associations (Pmeta < 5 × 10−5) with variants in 29 other regions, including TNFAIP3, PTTG1, PRDM1, DGKQ, FCGR2A, IRAK1BP1, ITSN2 and PHIP, among others. These results highlight the importance of genes that are involved in both innate and adaptive immunity in Sjögrens syndrome.


Annals of the Rheumatic Diseases | 2014

Comparison of the American-European Consensus Group Sjögren's syndrome classification criteria to newly proposed American College of Rheumatology criteria in a large, carefully characterised sicca cohort

Astrid Rasmussen; John A. Ice; He Li; Kiely Grundahl; Jennifer A. Kelly; Lida Radfar; Donald U. Stone; Kimberly S. Hefner; Juan-Manuel Anaya; Michael D. Rohrer; Rajaram Gopalakrishnan; Glen D. Houston; David M. Lewis; James Chodosh; John B. Harley; Pamela Hughes; Jacen S. Maier-Moore; Courtney G. Montgomery; Nelson L. Rhodus; A. Darise Farris; Barbara M. Segal; Roland Jonsson; Christopher J. Lessard; R. Hal Scofield; Kathy Moser Sivils

Abstract Objective To compare the performance of the American–European Consensus Group (AECG) and the newly proposed American College of Rheumatology (ACR) classification criteria for Sjögrens Syndrome (SS) in a well-characterised sicca cohort, given ongoing efforts to resolve discrepancies and weaknesses in the systems. Methods In a multidisciplinary clinic for the evaluation of sicca, we assessed features of salivary and lacrimal gland dysfunction and autoimmunity as defined by tests of both AECG and ACR criteria in 646 participants. Global gene expression profiles were compared in a subset of 180 participants. Results Application of the AECG and ACR criteria resulted in classification of 279 and 268 participants with SS, respectively. Both criteria were met by 244 participants (81%). In 26 of the 35 AECG+/ACR participants, the minor salivary gland biopsy focal score was ≥1 (74%), while nine had positive anti-Ro/La (26%). There were 24 AECG−/ACR+ who met ACR criteria mainly due to differences in the scoring of corneal staining. All patients with SS, regardless of classification, had similar gene expression profiles, which were distinct from the healthy controls. Conclusions The two sets of classification criteria yield concordant results in the majority of cases and gene expression profiling suggests that patients meeting either set of criteria are more similar to other SS participants than to healthy controls. Thus, there is no clear evidence for increased value of the new ACR criteria over the old AECG criteria from the clinical or biological perspective. It is our contention, supported by this report, that improvements in diagnostic acumen will require a more fundamental understanding of the pathogenic mechanisms than is at present available.


Arthritis & Rheumatism | 2016

X Chromosome Dose and Sex Bias in Autoimmune Diseases: Increased Prevalence of 47,XXX in Systemic Lupus Erythematosus and Sjögren's Syndrome.

Ke Liu; Biji T. Kurien; Sarah L. Zimmerman; Kenneth M. Kaufman; Diana H. Taft; Leah C. Kottyan; Sara Lazaro; Carrie A. Weaver; John A. Ice; Adam Adler; James Chodosh; Lida Radfar; Astrid Rasmussen; Donald U. Stone; David M. Lewis; Shibo Li; Kristi A. Koelsch; Ann Igoe; Mitali Talsania; Jay Kumar; Jacen S. Maier-Moore; Valerie M. Harris; Rajaram Gopalakrishnan; Roland Jonsson; James A. Lessard; Xianglan Lu; Jacques Eric Gottenberg; Juan-Manuel Anaya; Deborah S. Cunninghame-Graham; Andrew J.W. Huang

More than 80% of autoimmune disease predominantly affects females, but the mechanism for this female bias is poorly understood. We suspected that an X chromosome dose effect accounts for this, and we undertook this study to test our hypothesis that trisomy X (47,XXX; occurring in ∼1 in 1,000 live female births) would be increased in patients with female‐predominant diseases (systemic lupus erythematosus [SLE], primary Sjögrens syndrome [SS], primary biliary cirrhosis, and rheumatoid arthritis [RA]) compared to patients with diseases without female predominance (sarcoidosis) and compared to controls.


Annals of the Rheumatic Diseases | 2016

Interaction between innate immunity and Ro52-induced antibody causes Sjögren's syndrome-like disorder in mice

Barbara Szczerba; Paulina Kaplonek; Nina Wolska; Anna Podsiadlowska; Rybakowska Pd; Paromita Dey; Astrid Rasmussen; Kiely Grundahl; Kimberly S. Hefner; Donald U. Stone; Stephen K. Young; David M. Lewis; Lida Radfar; R. Hal Scofield; Kathy L. Sivils; Harini Bagavant; Umesh S. Deshmukh

Objectives Autoantibodies reactive with Ro52 are often found in sera of patients with Sjögrens syndrome (SS). This study was undertaken to investigate the role of Ro52-induced immune responses in pathogenesis of SS. Methods New Zealand Mixed (NZM) 2758 mice were immunised with Ro52 in alum adjuvant. Control mice were immunised either with maltose-binding protein or injected with alum alone. Mice were monitored for anti-Ro52 antibody, sialoadenitis and pilocarpine-induced salivation. Antibody binding to salivary gland (SG) cells was analysed in vivo and in vitro by immunofluorescence. Sera from immunised mice were passively transferred into untreated or alum injected NZM2758 mice. Results By day 30 post-immunisation, Ro52 immunised mice generated immunoprecipitating anti-Ro52 antibodies and they had the maximum drop in saliva production. Both Ro52 immunised and control mice showed evidence of mild sialoadenitis. However, only Ro52 immunised mice had antibody deposition in their SG. Passive transfer of Ro52-immune sera induced SG dysfunction in recipient mice, only if the recipients were primed with alum. In vitro, antibodies from Ro52-immune sera were internalised by a SG cell line and this uptake was inhibited by cytochalasin D treatment. Conclusions Our data show for the first time that antibodies induced by Ro52 are capable of inducing SG dysfunction, and that this phenomenon is dependent on the activation of innate immunity. The mouse model described in this study implies that autoantibody deposition in the SG might be an important step in the induction of xerostomia and pathogenesis of SS.


Rheumatology | 2016

Previous diagnosis of Sjögren's Syndrome as rheumatoid arthritis or systemic lupus erythematosus

Astrid Rasmussen; Lida Radfar; David M. Lewis; Kiely Grundahl; Donald U. Stone; C. Erick Kaufman; Nelson L. Rhodus; Barbara M. Segal; Daniel J. Wallace; Michael H. Weisman; Swamy Venuturupalli; Biji T. Kurien; Christopher J. Lessard; Kathy L. Sivils; R. Hal Scofield

OBJECTIVE The diagnosis of SS is often difficult and many patients are symptomatic for years with other diagnoses before confirmation of SS. Our aim was to determine whether overlapping clinical and serologic features with RA and SLE may in part drive the misdiagnoses. METHODS A total of 1175 sicca patients were evaluated in a multidisciplinary clinic and classified as having SS based on the American-European Consensus Group Criteria. They were interrogated for a past history of suspicion or diagnosis of RA, SLE or SSc. These diseases were confirmed or ruled out by applying the corresponding classification criteria if the patients responded affirmatively. RESULTS Of these, 524 (44.6%) subjects reported previous diagnosis or suspicion of RA, SLE or SSc, which was confirmed in 130 (24.8%) but excluded in 394 (75.2%) subjects. Of those previously diagnosed with another illness, 183 (34.9%) met the criteria for primary SS. RF was present in 70/191 patients with previous diagnosis of RA compared with 445/845 without a prior RA diagnosis (P = 3.38E-05), while 128/146 with a diagnosis of SLE had positive ANA compared with 622/881 without the diagnosis (P = 8.77E-06). Age also influenced former diagnoses: people with suspected RA were older than those without the diagnosis (P = 5.89E-06), while patients with SLE suspicion were younger (P = 0.0003). Interestingly, the previous diagnoses did not significantly delay a final classification of SS. CONCLUSION Among subjects classified as SS, the presence of a positive ANA or RF was associated with a previous, apparently erroneous diagnosis of SLE or RA, respectively.


Clinical Immunology | 2016

Klinefelter's syndrome (47,XXY) is in excess among men with Sjögren's syndrome

Valerie M. Harris; Rohan Sharma; Joshua Cavett; Biji T. Kurien; Ke Liu; Kristi A. Koelsch; Astrid Rasmussen; Lida Radfar; David M. Lewis; Donald U. Stone; C. Erick Kaufman; Shibo Li; Barbara M. Segal; Daniel J. Wallace; Michael H. Weisman; Swamy Venuturupalli; Jennifer A. Kelly; Marta E. Alarcón-Riquelme; Bernardo A. Pons-Estel; Roland Jonsson; Xianglan Lu; Jacques Eric Gottenberg; Juan-Manuel Anaya; Deborah S. Cunninghame-Graham; Andrew J.W. Huang; Michael T. Brennan; Pamela Hughes; Ilias Alevizos; Corinne Miceli-Richard; Edward C. Keystone

Primary Sjögrens syndrome (pSS) has a strong female bias. We evaluated an X chromosome dose effect by analyzing 47,XXY (Klinefelters syndrome, 1 in 500 live male births) among subjects with pSS. 47,XXY was determined by examination of fluorescence intensity of single nucleotide polymorphisms from the X and Y chromosomes. Among 136 pSS men there were 4 with 47,XXY. This was significantly different from healthy controls (1 of 1254 had 47,XXY, p=0.0012 by Fishers exact test) as well men with rheumatoid arthritis (0 of 363 with 47,XXY), but not different compared to men with systemic lupus erythematosus (SLE) (4 of 136 versus 8 of 306, Fishers exact test p=NS). These results are consistent with the hypothesis that the number of X chromosomes is critical for the female bias of pSS, a property that may be shared with SLE but not RA.


Jcr-journal of Clinical Rheumatology | 2012

Relation of sensory peripheral neuropathy in Sjögren syndrome to anti-Ro/SSA.

Amanda Kyle Scofield; Lida Radfar; John A. Ice; Evan Vista; Juan-Manuel Anaya; Glen D. Houston; David M. Lewis; Donald U. Stone; James Chodosh; Kimberly S. Hefner; Christopher J. Lessard; Kathy L. Moser; Robert Hal Scofield

Background Sjögren syndrome is a common, chronic autoimmune disease that typically produces inflammation and poor function of the salivary and lacrimal glands. Other organs can be affected, including the nervous system. Sensory peripheral neuropathy is a common manifestation of the disease. Methods Eight-eight patients attending a dry eyes–dry mouth clinic were diagnosed to have primary Sjögren syndrome and underwent a neurological examination. Anti-Ro (or SSA) and anti-La (or SSB) were determined using immunodiffusion as well as Inno-Lia and BioPlex ANA screen. Serum vitamin B12 levels were determined using an enzyme-linked microtiter plate assay. Results Twenty-seven (31%) of the 88 patients had peripheral neuropathy as defined by loss of light touch, proprioception, or vibratory sensation. Anti-Ro and anti-La were found by immunodiffusion in 12 patients, and 8 of these 12 had neuropathy (&khgr;2 = 8.46, P = 0.0036, odds ratio = 6.0 compared to those without precipitating anti-Ro and anti-La). Of the 27 patients with only anti-Ro by immunodiffusion, 13 (48.1%) had neuropathy (&khgr;2 = 5.587, P = 0.018, compared to those without anti-Ro). There was no relationship of the other, more sensitive measures of anti-Ro and anti-La to neuropathy. In addition, we found no association of serum vitamin B12 levels to neuropathy among these patients with Sjögren syndrome. Conclusions Sensory peripheral neuropathy is common among patients with Sjögren syndrome and is associated with the presence of anti-Ro and anti-La when determined by immunodiffusion.


Arthritis & Rheumatism | 2016

Brief Report: Patients With Primary Sjögren's Syndrome Who Are Positive for Autoantibodies to Tripartite Motif-Containing Protein 38 Show Greater Disease Severity.

Nina Wolska; Rybakowska Pd; Astrid Rasmussen; Michael Brown; Courtney G. Montgomery; Arkadiusz Klopocki; Kiely Grundahl; Robert Hal Scofield; Lida Radfar; Donald U. Stone; J.-M. Anaya; John A. Ice; Christopher J. Lessard; David M. Lewis; Nelson L. Rhodus; Rajaram Gopalakrishnan; Andrew J.W. Huang; Pamela Hughes; Michael D. Rohrer; Michael H. Weisman; Swamy Venuturupalli; Joel M. Guthridge; Judith A. James; Kathy L. Sivils; Harini Bagavant; Umesh S. Deshmukh

Autoantibodies reactive with Ro52 (tripartite motif−containing protein 21 [TRIM21]) are detected in 70% of patients with primary Sjögrens syndrome (SS). TRIM21 belongs to a 34‐member C‐IV family of TRIM proteins. Although autoantibodies against other TRIM proteins within the C‐IV family have been detected in the sera of patients with primary SS, their clinical relevance remains unclear. This study was undertaken to investigate the frequency of anti‐TRIM38 in patients with primary SS and evaluate its association with various clinical measures of the disease.


Arthritis & Rheumatism | 2015

Primary Sjögren's syndrome patients with autoantibodies against TRIM38 show greater severity of disease

Nina Wolska; Paulina Rybakowska; Astrid Rasmussen; Michael Brown; Courtney G. Montgomery; Arkadiusz G. Klopocki; Kiely Grundahl; Robert H. Scofield; Lida Radfar; Donald U. Stone; J.-M. Anaya; John A. Ice; Christopher J. Lessard; David M. Lewis; Nelson L. Rhodus; Rajaram Gopalakrishnan; Andrew J. W. Huang; Pamela Hughes; Michael D. Rohrer; Michael H. Weismann; Swamy Venuturupalli; Joel M. Guthridge; Judith A. James; Kathy L. Sivils; Harini Bagavant; Umesh S. Deshmukh

Autoantibodies reactive with Ro52 (tripartite motif−containing protein 21 [TRIM21]) are detected in 70% of patients with primary Sjögrens syndrome (SS). TRIM21 belongs to a 34‐member C‐IV family of TRIM proteins. Although autoantibodies against other TRIM proteins within the C‐IV family have been detected in the sera of patients with primary SS, their clinical relevance remains unclear. This study was undertaken to investigate the frequency of anti‐TRIM38 in patients with primary SS and evaluate its association with various clinical measures of the disease.


Arthritis & Rheumatism | 2015

X Chromosome Dose and Sex Bias in Autoimmune Diseases: Increased 47,XXX in Systemic Lupus Erythematosus and Sjögren's Syndrome

Ke Liu; Biji T. Kurien; Sarah L. Zimmerman; Kenneth M. Kaufman; Diana H. Taft; Leah C. Kottyan; Sara Lazaro; Carrie A. Weaver; John A. Ice; Adam Adler; James Chodosh; Lida Radfar; Astrid Rasmussen; Donald U. Stone; David M. Lewis; Shibo Li; Kristi A. Koelsch; Ann Igoe; Mitali Talsania; Jay Kumar; Jacen S. Maier-Moore; Valerie M. Harris; Rajaram Gopalakrishnan; Roland Jonsson; James A. Lessard; Xianglan Lu; Jacques-Eric Gottenberg; Juan-Manuel Anaya; Deborah S. Cunninghame-Graham; Andrew J.W. Huang

More than 80% of autoimmune disease predominantly affects females, but the mechanism for this female bias is poorly understood. We suspected that an X chromosome dose effect accounts for this, and we undertook this study to test our hypothesis that trisomy X (47,XXX; occurring in ∼1 in 1,000 live female births) would be increased in patients with female‐predominant diseases (systemic lupus erythematosus [SLE], primary Sjögrens syndrome [SS], primary biliary cirrhosis, and rheumatoid arthritis [RA]) compared to patients with diseases without female predominance (sarcoidosis) and compared to controls.

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Astrid Rasmussen

Oklahoma Medical Research Foundation

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Lida Radfar

University of Oklahoma

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Christopher J. Lessard

Oklahoma Medical Research Foundation

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John A. Ice

Oklahoma Medical Research Foundation

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Kiely Grundahl

Oklahoma Medical Research Foundation

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Kathy L. Sivils

Oklahoma Medical Research Foundation

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Biji T. Kurien

University of Oklahoma Health Sciences Center

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James Chodosh

Massachusetts Eye and Ear Infirmary

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Jennifer A. Kelly

Oklahoma Medical Research Foundation

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