SJÖGREN’S SYNDROME RESEARCH STUDIES

1.1 The Sjögren’s Clinic at UCSF
J.P. Whitcher, A. Wu, T. Daniels

The weekly Sjögren’s Clinic provides the basis for a long-term study with joint collaboration between the Department of Oral Medicine, the Department of Rheumatology, and the Proctor Foundation. Clinical and laboratory information is collected, as well as labial and salivary gland biopsy specimens on patients with the clinical diagnosis of Sjögren’s syndrome. The Sjögren’s Study Group has found that Sjögren’s syndrome is clearly associated with focal sialoadenitis in the labial salivary glands while other causes of keratitis sicca are associated with diffuse sialoadenitis. More than 650 patients with positive labial salivary gland biopsies, who have had complete ocular, oral, and rheumatologic work-ups, have been evaluated over the past 31 years. This study comprises the largest group of patients in the United States with pathological confirmation of the diagnosis of Sjögren’s syndrome.

Because this database includes both ocular and oral findings, Dr. Whitcher has published several papers on the correlation between the ocular and oral clinical findings with a detailed statistical analysis of the data. He is continuing his analysis of this large database to sort out the specific clinical features of Sjögren’s syndrome that are associated with the primary and secondary manifestations of the disease as well as the differences in association with gender and age. He is also looking into the diagnostic sensitivity and specificity of the different tests used to diagnose keratoconjunctivitis sicca in patients suspected of having Sjögren’s syndrome. In addition, he is looking at the ocular component of Sjögren’s syndrome separately in a 31-year retrospective clinical study.

In addition to analyzing this large database, Dr. Whitcher and colleagues are considering clinical studies such as follow-up of Sjögren’s syndrome patients, to determine whether or not they stabilize or continue to worsen with time. Because of the large number of patients who can be reached for follow-up, this study promises to answer some basic questions about the progression of the disease over several decades. There also exist several possibilities for clinical studies of various medications for the treatment of Sjögren’s syndrome, both symptomatic therapy and treatment of the underlying inflammatory component of the disease.

1.2 The Sjögren’s International Collaborative Clinical Alliance (SICCA)
J. Whitcher, E. Strauss, N. McNamara, A. Wu,
J. Greenspan, T. Daniels

In 2003 the Sjögren’s Study Group was awarded a $12 million five-year NIH grant to establish an international collaborative research center at UCSF to participate with four other international satellite Sjögren’s syndrome centers in Kanazawa, Japan; Beijing, China; Copenhagen, Denmark; and Buenos Aires, Argentina examining patients with primary Sjögren’s Syndrome, as well as related and non-related controls. This year a sixth center was added in London, England and a seventh center at Aravind Eye Hospital in Madurai, India is awaiting confirmation by the Indian Government. The coordinating center at UCSF is collecting all information pertaining to the examinations and a database of Sjögren’s syndrome patients is being created that includes tissue samples, serum, and bucal mucosal smears are collected from the patients and banked for future research. The criteria for the ocular diagnosis of primary Sjögren’s have been standardized and the scoring system has been validated by data from a cohort of 736 patients. These ocular diagnostic criteria that are quantitative and validated by data are the first ocular scoring system for Sjögren’s patients that is data based. The scoring system has also been designed to be simple and user friendly so that it will be universally accepted.

Tissue samples collected from labial salivary gland (LSG) biopsies, bucal mucosal smears, serum samples, tear samples, and conjunctival impression for RNA will be made available to researchers on a competitive basis to investigate the genetic characteristics of Sjögren’s syndrome. It is anticipated that six thousand patients and controls will be recruited for the study during the five-year period. The Sjögren’s Study Group makes site visits to all of the international sites annually to standardize examination procedures, data collection and transmission procedures, methods for doing surgical procedures on LSGs, and methods for collection of other materials for genetic analysis. We anticipate that the data collected in the SICCA Study will provide the impetus for many secondary research projects investigating the diagnosis, immunology, genetics, and treatment of Sjögren’s syndrome, with the ultimate goal of finding a cure.