ACR Meeting Abstracts

ACR Meeting Abstracts

  • Home
  • Meetings Archive
    • 2023 ACR/ARP PRSYM
    • ACR Convergence 2022
    • ACR Convergence 2021
    • ACR Convergence 2020
    • 2020 ACR/ARP PRSYM
    • 2019 ACR/ARP Annual Meeting
    • 2018 ACR/ARHP Annual Meeting
    • 2017-2009 Meetings
    • Download Abstracts
  • Keyword Index
  • Advanced Search
  • Your Favorites
    • Favorites
    • Login
    • View and print all favorites
    • Clear all your favorites
  • Meeting Resource Center

Abstract Number: 2974

B Cell Binding Autoreactive VH4.34 Antibodies Are Specific to Lupus, Consist of Diverse Isotypes, and Are Associated with High Disease Activity and Lupus Nephritis

Scott Jenks1, Joseph Marcus2, Kevin Cashman1 and Ignacio Sanz3, 1Emory University School of Medicine and Lowance Center for Human Immunology, Atlanta, GA, 2San Antonio Uniformed Services Health Education Consortium, San Antonio, TX, 3Rheumatology and Lowance Center for Human Immunology, Emory University School of Medicine and Lowance Center for Human Immunology, Atlanta, GA

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: autoantibodies, B cells, nephritis and tolerance, SLE

  • Tweet
  • Email
  • Print
Session Information

Date: Wednesday, November 8, 2017

Session Title: Systemic Lupus Erythematosus – Human Etiology and Pathogenesis II

Session Type: ACR Concurrent Abstract Session

Session Time: 11:00AM-12:30PM

Background/Purpose: SLE is characterized by the dysregulation of humoral immunity including high levels of autoreactive IgG VH4.34 antibodies recognized by the rat anti-human idiotypic antibody 9G4 (9G4+). VH4.34 antibodies have a germ line encoded anti-self specificity for blood antigen glycolipids and glycolipid epitopes of the B220 isoform of CD45 expressed on naïve B cells. As a consequence, naïve B cells from SLE patients can have high levels of 9G4 staining ex vivodue to surface bound VH4.34 antibodies. Serum 9G4+ IgG is correlated with high disease activity, lupus nephritis and anti-dsDNA. The role of B cell binding (BCB) 9G4+ in lupus pathogenesis and its potential clinical correlates is unclear.

Methods: 161 SLE (4 or more ACR criteria) patients were analyzed, including 24 patients with active nephritis. SLE patients were compared to 30 healthy controls or 15 RA, 15 Dermatomyositis, 26 scleroderma, and 7 pSS patients analyzed as autoimmune controls. 9G4+ BCB was measured ex vivo by flow cytometry and BCB was quantified as the ratio of the median fluorescence intensity of naïve B cells to that of switched memory. The resulting B cell binding ratio (BR) ranged from 1 (no binding) to 20 (very high binding) patients with a BR higher than 2.5 were considered positive. 9G4+ IgG, IgM, and IgA were measured by ELISA, capturing with the rat monoclonal 9G4 and detecting with goat anti-human IgG, IgM, or IgA.

Results:

BCB binding was highly specific for SLE as 33% of SLE patients were BCB positive compared to only 1.6% of autoimmune control patients and none of the HCD. Lupus patients with high disease activity or active nephritis were significantly more likely to have BCB than patients with low disease activity (47% and 54% as compared to 24% for low disease activity). When we compared BR to serum 9G4+ IgG concentration we found only a weak correlation (p=0.04, r=0.26). However, SLE patients had elevated 9G4+ IgM and IgA and the concentration of these isotypes was more strongly correlated with BCB (IgM p >0.001, r= 0.586) (IgA p>0.001, r=0.4602 ). IgA BCB was demonstrated directly by the detection of both surface 9G4 and IgA staining of healthy control donor naïve B cells after incubation with serum from an SLE patient. Patients with high BR had higher disease activity (p=0.021) and were more likely to have a history lupus nephritis (p=0.002) but this was not true for serum 9G4+ isotypes measure in either isolation or combination.

Conclusion:

The degree of B cell bound 9G4+ in some SLE patients is striking. Here we show that this auto-reactivity is specific to lupus and is more common in patients with active disease and active lupus nephritis. Interestingly, this association between B cell bound 9G4+ and disease activity is stronger than the association between serum 9G4+ IgG. As suggested by our data, this may be consequence of BCB measuring 9G4+ antibodies of multiple isotypes. The combination of IgA and IgG anti-dsDNA is more predictive of disease activity than either isotype alone and the same may be true for BCB 9G4+. In this light our finding that 9G4+ IgA is elevated in SLE patients and can bind B cells is intriguing. BCB 9G4+ may be a useful assay for stratifying SLE patients into clinically and immunologically distinct groups in future clinical and mechanistic studies.


Disclosure: S. Jenks, None; J. Marcus, None; K. Cashman, None; I. Sanz, None.

To cite this abstract in AMA style:

Jenks S, Marcus J, Cashman K, Sanz I. B Cell Binding Autoreactive VH4.34 Antibodies Are Specific to Lupus, Consist of Diverse Isotypes, and Are Associated with High Disease Activity and Lupus Nephritis [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/b-cell-binding-autoreactive-vh4-34-antibodies-are-specific-to-lupus-consist-of-diverse-isotypes-and-are-associated-with-high-disease-activity-and-lupus-nephritis/. Accessed May 29, 2023.
  • Tweet
  • Email
  • Print

« Back to 2017 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/b-cell-binding-autoreactive-vh4-34-antibodies-are-specific-to-lupus-consist-of-diverse-isotypes-and-are-associated-with-high-disease-activity-and-lupus-nephritis/

Advanced Search

Your Favorites

You can save and print a list of your favorite abstracts during your browser session by clicking the “Favorite” button at the bottom of any abstract. View your favorites »

© COPYRIGHT 2023 AMERICAN COLLEGE OF RHEUMATOLOGY

Wiley

  • Home
  • Meetings Archive
  • Advanced Search
  • Meeting Resource Center
  • Online Journal
  • Privacy Policy
  • Permissions Policies
  • Cookie Preferences