NIDCR Sjögren's International Collaborative Clinical Alliance (SICCA)

The Sjögren's International Collaborative Clinical Alliance (SICCA) is a multisite observational cohort study that recruited a large cohort of geographically diverse participants. Enrollment of participants began in late 2004 at five (one domestic and four international) sites, in which all groups used the same protocol-directed methods to provide uniform evaluations; collect oral, ocular, and rheumatologic data; and collect specimens. The sites were located at the University of Buenos Aires, Argentina; Peking Union Medical College, Beijing, China; Rigshopitalet (formerly at Glostrup Hospital), Copenhagen, Denmark; Kanazawa Medical University, Ishikawa, Japan; King's College, London, UK (joined in 2007); and the University of California, San Francisco (UCSF). In 2009, Aravind Eye Hospital, Madurai, India; Johns Hopkins University, Baltimore, MD; and University of Pennsylvania, Philadelphia, PA were added as additional SICCA sites. UCSF is the coordinating center for SICCA. All specimens and data collected for SICCA are housed at UCSF. To facilitate the research focused on understanding the genetics of Sjögren'sSjögren's syndrome, high-density SNP genotype data and SICCA clinical information are being made available to the research community. This includes participants recruited from all SICCA research groups (RG). These participants (3,382), blood relatives (439), and unrelated healthy controls (25) had their whole blood or saliva sample (Oragene) extracted for DNA for the GWAS at the UCSF DNA Bank. Eighty eight percent of the participants are women, most are of European or Asian ancestry and the median age is 55. To assess potential batch effects when doing case-control comparisons using planned external controls, 30 DNA samples from each of three studies were genotyped with SICCA DNA samples: The Genetic Architecture of Smoking and Smoking Cessation - Collaborative Genetic Study of Nicotine Dependence (COGEND) - PI: Laura Bierut. NEI-Age-related disease study (AREDS) - Genetic Variation in Refractive Error Substudy - PI: Dwight Stambolian. Controls from the National Institute of Mental Health's (NIMH's) Human Genetics Initiative. Genome-Wide Association Study of Schizophrenia - PI: Pablo V. Gejman. Molecular Genetics of Schizophrenia - nonGAIN Sample (MGS_nonGAIN) - PI: Pablo V. Gejman. Genotyping was performed at the Johns Hopkins University Center for Inherited Disease Research (CIDR). Data quality control, dbGaP preparation and posting, and imputation to 1000 Genomes to increase SNP density was performed by the Center for Biomedical Statistics at the University of Washington. Data analysis was performed at UCSF using software PLINK, EIGENSOFT, and SNPTEST.]]>
Inclusion Criteria A person must have at least one of the following characteristics: A complaint of dry eyes or dry mouth, or both A previous diagnosis of primary Sjögren's Syndrome (pSS) (with records available at the institution study site) Have abnormal serology suggestive of systemic autoimmune disorder (i.e., elevated RF, ANA, anti-SSA, or anti-SSB) Bilateral parotid enlargement consistent with SS Multiple cervical or incisal dental caries, in the absence of other risk factors A diagnosis or symptoms of secondary Sjögren's with a confirmed diagnosis of rheumatoid arthritis or systemic lupus erythematosus. Be 21 years or older Have signed an IRB consent form agreeing to the terms of the study Exclusion Criteria < 21 years of age. Known diagnoses of: Hepatitis C infection HIV infection Sarcoidosis Amyloidosis Graft versus host disease Cicatrizing conjunctivitis (e.g. from trachoma, Stevens-Johnson syndrome, pemphigoid, drug induced pseudo-pemphigoid, or chemical ocular burns) Pre-existing lymphoma in patients with no prior diagnosis of SS Past head and neck radiation treatment. Being treated for glaucoma with daily eye drops, has had corneal surgery to improve vision in the last five years, has had cosmetic surgery on eyelids in the past five years, or wears contact lenses but unwilling not to wear contact lenses for 7 days prior to their baseline visit. Physical or mental condition interfering with the successful participation in this study. Known diagnosis of autoimmune connective tissue diseases (i.e., mixed connective tissue disease; scleroderma). Participants with a diagnosis of or symptoms of secondary Sjögren's syndrome and a confirmed diagnosis of rheumatoid arthritis or systemic lupus erythematous were eligible. ]]>
The Sjögren's International Collaborative Clinical Alliance (SICCA) was funded under a NIH contract in 2003 to: Establish an International Research Registry Network for Sjögren's syndrome (SS); Establish a set of standardized classification criteria for Sjögren's syndrome that will be used by all countries for the purpose of research, prevention, diagnosis, and treatment of Sjögren's syndrome; Collect, process, store, ship and analyze clinical and biological specimens from patients and families with Sjögren's syndrome; and Disseminate to researchers coded clinical information and biological specimens from patients with Sjögren's syndrome and their families. SICCA is a multisite observational study that includes a large cohort of geographically diverse participants. UCSF is the SICCA coordinating center and in 2004 the following institutions were enlisted to help achieve our contract goals: University of Buenos Aires, Argentina Peking Union Medical College, Beijing, China Rigshopitalet (formerly at Glostrup Hospital), Copenhagen, Denmark Kanazawa Medical University, Ishikawa, Japan In 2007, King's College, Dental Institute at Guy's, London, UK was added to help us achieve our enrollment goals. Our contract was extended for four years from September 2009 - September 2013. During this extension period, three new study sites were added to SICCA. The new research groups (RG) were located at Johns Hopkins, Baltimore, MD; University of Pennsylvania, Philadelphia, PA; and the Aravind Eye Hospital in Madurai, India. Standardized questionnaires were developed to screen potential participants, collect information on medical history, demographics, tobacco use history, general physical and emotional health, reproductive and hormonal history for women only, and symptoms affecting the mouth and eyes. For the non-English speaking RGs, forms were translated and back translated to English for quality control purposes at each site. Objective evaluation of salivary function was done by collecting unstimulated whole and stimulated parotid saliva at the initial (baseline) visit and recall visit (occurring after two years, however after December 31, 2011 recall participants were no longer seen). Objective evaluation of lacrimal function at the initial and follow-up visits was performed using Schirmer test, Lissamine Green staining, and tear break-up time with .5% fluorescein. Objective evaluation of lymphocytic infiltration of the minor salivary glands is performed by histological analysis of labial salivary glands (LSG) biopsies obtained within three years prior to the initial visit and at recall. Serum autoantibody profiles for SS-A, SS-B, IgG, IgA, IgM, rheumatoid factor, ANA with titer and pattern if positive, C3, C4, Hepatitis C, and CBC with differentials was collected at baseline and follow-up visits. Participants had a physical exam by a rheumatologist or nurse practitioner during baseline and recall visits. Specimens such as LSG (frozen and paraffin-embedded), parotid and whole saliva, sera, tears, conjunctival imprints, and whole blood for DNA extraction were collected at baseline and recall visits, and stored at the UCSF SICCA Specimen Bank for the dissemination phase of this contract. UCSF was the only research group that collects plasma and PBMCs from their SICCA participants. Participants had a physical exam by a rheumatologist or nurse practitioner during baseline and recall visits. In addition, there was a cross-sectional study of blood-related family members for participants that fit SICCA's 'working definition' of SS. Parents and/or siblings of participants 'diagnosed' as pSS or sSS were asked if they were willing to fill out a questionnaire and provide a blood or saliva (OrageneTM) sample. Participants with SS were asked to contact other blood relatives that are diagnosed or suspected of having SS. During the period of 2004-2010, Dr. John Greenspan was PI and Troy Daniels was co-PI of SICCA. In mid-2010, Dr. Caroline Shiboski became PI and Dr. Lindsey Criswell is co-PI of SICCA.]]>