Dataset Information

Choroid plexus tertiary lymphoid structures in lupus: a novel neuro-immune interface

ABSTRACT: The central nervous system manifestations of systemic lupus erythematosus (SLE) remain poorly understood, confounding physician treatment options and leaving patients with little options beyond empirical remedies. We utilized a well-established model of both the systemic and neuropsychiatric manifestations of SLE in an attempt to further understand which immune effectors may be responsible for central nervous system (CNS) disease. We found that a mixed cellular infiltrate in the choroid plexus of these mice represented a tertiary lymphoid structure with in-situ somatic hypermutation and class switch recombination. We further found that this process was driven by cytokine signaling sourced within the CNS that could be abrogated by treatment with biological therapeutics. Therefore, inconsistencies in previous work to determine which neuropathic autoantibodies are involved in the progression of neuropsychiatric lupus may have been lacking, as the source of these autoantibodies are intra-cranial, with limited systemic distribution.

ORGANISM(S): Mus musculus

PROVIDER: GSE99030 | GEO | 2019/06/17

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Introduction: Pediatric systemic lupus erythematosus (pSLE) patients often initially present with more active and severe disease than adults, including a higher frequency of lupus nephritis. Specific autoantibodies, including anti-C1q, anti-DNA and anti-alpha-actinin, have been associated with kidney involvement in SLE, and DNA antibodies are capable of initiating early stage lupus nephritis in severe combined immunodeficiency (SCID) mice. Over 100 different autoantibodies have been described in SLE patients, highlighting the need for comprehensive autoantibody profiling. Knowledge of the antibodies associated with pSLE and proliferative nephritis will increase the understanding of SLE pathogenesis, and may aid in monitoring patients for renal flare. Methods: We used autoantigen microarrays composed of 140 recombinant or purified antigens to compare the serum autoantibody profiles of new-onset pSLE patients (n=45) to healthy controls (n=17). We also compared pSLE patients with biopsy-confirmed class III or IV proliferative nephritis (n=23) and without significant renal involvement (n=18). We performed ELISA with selected autoantigens to validate the microarray findings. We created a multiple logistic regression model, based on the ELISA and clinical information, to predict whether a patient had proliferative nephritis, and used a validation cohort (n=23) and longitudinal samples (88 patient visits) to test its accuracy. Results: Fifty autoantibodies were at significantly higher levels in the sera of pSLE patients compared to healthy controls, including anti-B-cell activating factor (BAFF). High levels of anti-BAFF were associated with active disease. Thirteen serum autoantibodies were present at significantly higher levels in pSLE patients with proliferative nephritis than those without, and we confirmed five autoantigens (dsDNA, C1q, collagens IV & X and aggrecan) by ELISA. Our model, based on ELISA measurements and clinical variables, correctly identified patients with proliferative nephritis with 91% accuracy. Conclusions: Autoantigen microarrays are an ideal platform for identifying autoantibodies associated with both pSLE and specific clinical manifestations of pSLE. Using multiple regression analysis to integrate autoantibody and clinical data permits accurate prediction of clinical manifestations with complex etiologies in pSLE.

Dataset Information

Choroid plexus tertiary lymphoid structures in lupus: a novel neuro-immune interface

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets