Rohan Sharma1,2, Kaustubh S Chaudhari1,2, Biji T Kurien1,2, Kiely Grundahl1,2, Lida Radfar1,2, David M Lewis1,2, Christopher J Lessard1,2, He Li1,2, Astrid Rasmussen1,2, Kathy L Sivils1,2, R Hal Scofield3,4. 1. From the Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma; Department of Neurology, University of Arkansas Medical Sciences Center, Little Rock, Arkansas; Medical and Research Services, Oklahoma City Department of Veterans Affairs Medical Center; Departments of Medicine and Pathology, University of Oklahoma Health Sciences Center; College of Dentistry, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA. 2. R. Sharma, MBBS, Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Department of Neurology, University of Arkansas Medical Sciences Center; K.S. Chaudhari, MBBS, Medical and Research Services, Oklahoma City Department of Veterans Affairs Medical Center; B.T. Kurien, PhD, Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Medical and Research Services, Oklahoma City Department of Veterans Affairs Medical Center, Departments of Medicine and Pathology, University of Oklahoma Health Sciences Center; K. Grundahl, BS, Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation; L. Radfar, DDS, College of Dentistry, University of Oklahoma Health Sciences Center; D.M. Lewis, DDS, College of Dentistry, University of Oklahoma Health Sciences Center; C.J. Lessard, PhD, Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation; H. Li, PhD, Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation (currently Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas); A. Rasmussen, MD, PhD, Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation; K.L. Sivils, PhD, Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation; R.H. Scofield, MD, Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Medical and Research Services, Oklahoma City Department of Veterans Affairs Medical Center, Departments of Medicine and Pathology, University of Oklahoma Health Sciences Center. 3. From the Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma; Department of Neurology, University of Arkansas Medical Sciences Center, Little Rock, Arkansas; Medical and Research Services, Oklahoma City Department of Veterans Affairs Medical Center; Departments of Medicine and Pathology, University of Oklahoma Health Sciences Center; College of Dentistry, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA. hal-scofield@omrf.ouhsc.edu. 4. R. Sharma, MBBS, Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Department of Neurology, University of Arkansas Medical Sciences Center; K.S. Chaudhari, MBBS, Medical and Research Services, Oklahoma City Department of Veterans Affairs Medical Center; B.T. Kurien, PhD, Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Medical and Research Services, Oklahoma City Department of Veterans Affairs Medical Center, Departments of Medicine and Pathology, University of Oklahoma Health Sciences Center; K. Grundahl, BS, Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation; L. Radfar, DDS, College of Dentistry, University of Oklahoma Health Sciences Center; D.M. Lewis, DDS, College of Dentistry, University of Oklahoma Health Sciences Center; C.J. Lessard, PhD, Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation; H. Li, PhD, Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation (currently Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas); A. Rasmussen, MD, PhD, Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation; K.L. Sivils, PhD, Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation; R.H. Scofield, MD, Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Medical and Research Services, Oklahoma City Department of Veterans Affairs Medical Center, Departments of Medicine and Pathology, University of Oklahoma Health Sciences Center. hal-scofield@omrf.ouhsc.edu.
Abstract
OBJECTIVE: Primary Sjögren syndrome (SS) is characterized by a focal lymphocytic infiltrate in exocrine glands. We describe patients who lacked this key feature. METHODS: We evaluated patients with sicca in a comprehensive clinic at which medical, dental, and ophthalmological examinations were performed. All subjects underwent a minor salivary gland biopsy with focus score calculation. Extraglandular manifestations were also determined. We categorized subjects as high, intermediate, or low in terms of expression of interferon (IFN)-regulated genes. RESULTS: About 20% (51 of 229, 22%) of those classified as having primary SS had a focus score of zero. Compared to those with anti-Ro positivity and a focus score > 1.0, the patients with focus score of zero (who by classification criteria must be anti-Ro-positive) were statistically less likely to have anti-La (or SSB) and elevated immunoglobulin, as well as less severe corneal staining. The focus score zero patients were less likely to have elevated expression of IFN-regulated genes in peripheral blood mononuclear cells than anti-Ro-positive SS patients with a focal salivary infiltrate. CONCLUSION: There are only a few clinical differences between patients with primary SS with focus score zero and those with both anti-Ro and a focus score > 1.0. The small subset of focus score zero patients tested did not have elevated expression of IFN-regulated genes, but did have systemic disease. Thus, extraglandular manifestations are perhaps more related to the presence of anti-Ro than increased IFN. This may have relevance to pathogenesis of SS.
OBJECTIVE: Primary Sjögren syndrome (SS) is characterized by a focal lymphocytic infiltrate in exocrine glands. We describe patients who lacked this key feature. METHODS: We evaluated patients with sicca in a comprehensive clinic at which medical, dental, and ophthalmological examinations were performed. All subjects underwent a minor salivary gland biopsy with focus score calculation. Extraglandular manifestations were also determined. We categorized subjects as high, intermediate, or low in terms of expression of interferon (IFN)-regulated genes. RESULTS: About 20% (51 of 229, 22%) of those classified as having primary SS had a focus score of zero. Compared to those with anti-Ro positivity and a focus score > 1.0, the patients with focus score of zero (who by classification criteria must be anti-Ro-positive) were statistically less likely to have anti-La (or SSB) and elevated immunoglobulin, as well as less severe corneal staining. The focus score zero patients were less likely to have elevated expression of IFN-regulated genes in peripheral blood mononuclear cells than anti-Ro-positive SS patients with a focal salivary infiltrate. CONCLUSION: There are only a few clinical differences between patients with primary SS with focus score zero and those with both anti-Ro and a focus score > 1.0. The small subset of focus score zero patients tested did not have elevated expression of IFN-regulated genes, but did have systemic disease. Thus, extraglandular manifestations are perhaps more related to the presence of anti-Ro than increased IFN. This may have relevance to pathogenesis of SS.
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