Date: Monday, October 22, 2018
Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
Background/Purpose: Anti-RNP Autoimmunity is associated with multiple manifestations of vasculopathy, including Raynaud’s Phenomenon (RP) and Pulmonary Hypertension (PH). We have previously linked anti-K10 antibodies to RP. However, since RP typically presents early in disease whereas PH is typically a late manifestation of disease, we hypothesize that they are mediated by differing factors.
Methods: Using IRB-approved studies on a human cohort of anti-RNP autoimmunity, as well as IACUC-approved protocols to study murine models of anti-RNP-associated autoimmunity, we performed studies to assess the contribution of autoantibodies, T cell-mediated autoimmunity, and cellular components of the innate immune system to the development and persistence of anti-RNP-associated RP and PH.
Results: In a cohort of 130 patients with anti-RNP autoimmunity, 19 patients (15%) had PH (by criteria and/or clinical diagnosis). RP was present in 79/111 patients without PH (71%),but only in 10/19 patients with PH (53%, Fisher’s p = 0.12). Anti-K10 antibodies were present in 7/19 PH patients (37%) but in 67/111 not PH patients (60%, p = 0.08). Thus, trends disfavored associations between PH and either RP+ or anti-K10+ status.
Spontaneously autoimmune Trex1-deficient mice developed anti-K10 antibodies only concurrent with or after the development of anti-RNP antibodies (12/38 RNP+ vs 0/13 RNP- mice, p = 0.02). Spontaneous ischemic thermoregulatory tissue loss was observed infrequently (2/12), but only in the subset of mice that developed anti-K10 antibodies. However, up to 18 weeks after the development of anti-RNP antibodies, there were no differences in (normal) BNP levels observed in mice with versus without anti-K10 antibodies.
In contrast, study mice that received CD11c+ spleen cells from RNP+ syngeneic donors uniformly developed RNP+ status with increased serum BNP levels and increased right heart pressures by direct catheter measurements, but without clinical evidence of RP. Treatment with a small molecule antigen presenting cell toxin targeted to CD11b+ cells rapidly reversed established pulmonary hypertension in 4/5 (80%) mice (vs 0/6 controls, p = 0.02). Likewise, an RNP antigen-specific T cell vaccination induced reductions in BNP levels in 6/9 treated mice with induced anti-RNP lung disease, with substantially lower BNP values than in mock-treated controls (Mann-Whitney p = 0.007) while causing no changes in anti-RNP antibody levels.
Conclusion: While anti-K10 antibodies may be sufficient to induce RP in anti-RNP autoimmunity, anti-RNP-associated PH shows trends toward a negative association with anti-K10 and instead may be mediated by T cells and cellular innate immune constituents.
To cite this abstract in AMA style:Harlow L, Wang Y, Zang Y, Gupta V, Young K, Huang J, Aubourg B, Greidinger E. Distinct Pathways in Anti-RNP-Associated Pulmonary Hypertension and Anti-RNP-Associated Raynaud’s Phenomenon [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 10). https://acrabstracts.org/abstract/distinct-pathways-in-anti-rnp-associated-pulmonary-hypertension-and-anti-rnp-associated-raynauds-phenomenon/. Accessed March 18, 2019.
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