Autoantibodies are typically present many years before the diagnosis of SLE. Furthermore, the appearance of autoantibodies in patients with SLE tends to follow a predictable course, with a progressive accumulation of specific autoantibodies before the onset of SLE, while patients are still asymptomatic.

No abstract

The Defense Medical Surveillance System (DMSS) is the central repository of medical surveillance data for the US armed forces. The DMSS integrates data from sources worldwide in a continuously expanding relational database that documents the military and medical experiences of service members throughout their careers. The Department of Defense Serum Repository (DoDSR) is a central archive of sera drawn from service members for medical surveillance purposes. Currently, the DMSS contains data relevant to more than 7 million individuals who have served in the armed forces since 1990, and the DoDSR contains more than 27 million specimens that are linkable to data in the DMSS. Recent applications of the DMSS and DoDSR provide glimpses of the capabilities and uses of comprehensive public health surveillance systems.

Corresponding author: V. Michael Holers, MD, Division of Rheumatology, University of Colorado at Denver and Health Sciences Center, Barbara Davis Center, 1775 North Ursula Street, Aurora, Colorado 80045, Phone: (303) Fax: (303) 724-7581, Michael.Holers@uchsc.edu. Address for reprint requests: Same as above * These two authors contributed equally to the study. COMPETING INTERESTSThe authors declare that they have no competing interests. AUTHORS' CONTRIBUTIONSDM participated in the design and analysis of this study and the writing of this manuscript. KD participated in the analysis of data and preparation of manuscript. LP participated in the analysis of samples and data and preparation of manuscript. AB and AL contributed statistical expertise in the analysis of data for this manuscript. CW participated in subject evaluation and determination of eligibility for this study MR participated in the design of this study and procurement of the serum samples for analysis WG participated in the design of this study and procurement of the serum samples for analysis, as well as subject evaluation and determination of eligibility for this study. JN participated in the design and analysis of this study and preparation of manuscript. VMH participated in the design and analysis of this study, antibody testing, and manuscript preparation. DISCLAIMERThe views expressed in this abstract are those of the authors and do not reflect the official policy of the Department of the Army, Department of Defense, or U.S. Government.The Corresponding Author has the right to grant on behalf of all authors and does grant on behalf of all authors, an exclusive license (or non-exclusive for government employees) on a worldwide basis to the BMJ Publishing Group Ltd and its Licensees to permit this article to be published in Annals of Rheumatic Diseases editions and any other BMJPGL products to exploit all subsidiary rights, as set out in our license http://ard.bmjjournals.com/ifora/licence.pdf. Objectives-This study investigated factors that may influence the prevalence and timing of appearance of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies during the pre-clinical phase of rheumatoid arthritis (RA) development. NIH Public AccessMethods-243 serial pre-diagnosis serum samples from 83 subjects with RA were examined for the presence of RF and anti-CCP antibodies.Results-57% and 61% of subjects had at least one pre-diagnosis sample positive for RF or anti-CCP, respectively. Gender and race were not significantly associated with the prevalence or timing of pre-clinical antibody appearance. Pre-clinical anti-CCP positivity was strongly associated with the development of erosive RA (OR 4.64; 95% CI 1.71-12.63; p=0.003), but RF was not (p=0.11). Additionally, as age at the time of diagnosis of RA increased the duration of pre-diagnosis antibody positivity for RF and anti-CCP increased, with the longest duration of preclinical antibody positivity seen in patients diagnosed with RA over the age of 40. In ...

Increased exposure to p,p'-DDE may be associated with the risk of both seminomatous and nonseminomatous TGCTs, whereas exposure to chlordane compounds and metabolites may be associated with the risk of seminoma. Because evidence suggests that TGCT is initiated in very early life, it is possible that exposure to these persistent organic pesticides during fetal life or via breast feeding may increase the risk of TGCT in young men.

Objective. To determine whether antiphospholipid antibodies (aPL) occur before the diagnosis of systemic lupus erythematosus (SLE) and before initial clotting events, and whether their presence early in the disease course influences clinical outcome.Methods. Serum samples obtained from 130 lupus patients before and after SLE diagnosis were screened for IgG and IgM aPL using an anticardiolipin (aCL) enzyme-linked immunosorbent assay. Medical records of all patients were carefully reviewed for data on the time of onset of SLE features meeting clinical criteria and on disease manifestations.Results. Twenty-four patients (18.5%) were positive for IgG and/or IgM aCL prior to SLE diagnosis. Anticardiolipin antibodies appeared from 7.6 years prior to SLE diagnosis to within the same month as SLE diagnosis, with a mean onset occurring 3.0 years before SLE diagnosis. Additionally, aCL presence early in the disease process seemed to predict a more severe clinical outcome; these patients eventually met an average of 6.1 of the 11 classification criteria for SLE, compared with 4.9 criteria for other patients (P < 0.001). The early aCL-positive population also had more frequent renal disease, central nervous system disease, thrombocytopenia, and clotting events. In this population, aCL preceded initial thrombotic events by a mean of 3.1 years.Conclusion. Anticardiolipin antibodies in SLE patients tend to precede initial clotting events by several years. Furthermore, the presence of early, prediagnosis aPL seems to herald a more varied, severe clinical course with earlier onset in patients with SLE.

The etiology of testicular germ cell tumors (TGCTs) is poorly understood, with cryptorchidism and family history being the only well-established risk factors. Body size, age at puberty, and dairy consumption, however, have been suggested to be related to TGCTs. To clarify the relation of these variables to TGCT risk and to one another, the authors analyzed data from 767 cases and 928 controls enrolled in the Servicemen's Testicular Tumor Environmental and Endocrine Determinants Study (2002-2005). Overall, increased height was significantly related to risk (odds ratio (OR) = 1.83, 95% confidence interval (CI): 1.36, 2.45), though body mass index was not (OR = 1.06, 95% CI: 0.66, 1.69). There was no association with age at puberty, based on ages at first shaving (OR = 1.29, 95% CI: 0.96, 1.73), voice changing (OR = 0.97, 95% CI: 0.71, 1.32), and nocturnal emissions (OR = 1.00, 95% CI: 0.73, 1.37). Similarly, there was no relation with dairy consumption at any age between birth and 12th grade. These results suggest that height is a risk factor for TGCTs, but the relation is unlikely explained by childhood dairy consumption. As adult height is largely determined in the first 2 years of life, increased attention to events in this interval may help elucidate the etiology of TGCTs.

Context Infection with Epstein-Barr virus (EBV) has been associated with an increased risk of multiple sclerosis (MS), but the temporal relationship remains unclear. Objective To determine whether antibodies to EBV are elevated before the onset of MS. Design, Setting, and Population Nested case-control study conducted among more than 3 million US military personnel with blood samples collected between 1988 and 2000 and stored in the Department of Defense Serum Repository. Cases were identified as individuals granted temporary or permanent disability because of MS. For each case (n=83), 2 controls matched by age, sex, race/ethnicity, and dates of blood sample collection were selected. Main Outcome Measures Antibodies including IgA against EBV viral capsid antigen (VCA) and IgG against VCA, nuclear antigens (EBNA complex, EBNA-1, and EBNA-2), diffuse and restricted early antigens, and cytomegalovirus. Results The average time between blood collection and MS onset was 4 years. The strongest predictors of MS were serum levels of IgG antibodies to VCA or EBNA complex. The risk of MS increased monotonically with these antibody titers; relative risk (RR) in persons in the highest category of VCA (Ն2560) compared with those in the lowest (Յ160) was 19.7 (95% confidence interval [CI], 2.2-174; P for trend=.004). For EBNA complex titers, the RR for those in the highest category (Ն1280) was 33.9 (95% CI, 4.1-283; P for trend Ͻ.001) vs those in the lowest category (Յ40). Similarly strong positive associations between EBV antibodies and risk of MS were already present in samples collected 5 or more years before MS onset. No association was found between cytomegalovirus antibodies and MS. Conclusion These results suggest a relationship between EBV infection and development of MS.