Borrelia-specific antibody profiles and complement deposition in joint fluid distinguish antibiotic-refractory from -responsive Lyme arthritis

Kathryn A Bowman; Christine D Wiggins; Elizabeth DeRiso; Steffan Paul; Klemen Strle; John A Branda; Allen C Steere; Douglas A Lauffenburger; Galit Alter

doi:10.1016/j.isci.2024.108804

Borrelia-specific antibody profiles and complement deposition in joint fluid distinguish antibiotic-refractory from -responsive Lyme arthritis

iScience. 2024 Jan 4;27(2):108804. doi: 10.1016/j.isci.2024.108804. eCollection 2024 Feb 16.

Authors

Kathryn A Bowman^{1

2}, Christine D Wiggins³, Elizabeth DeRiso¹, Steffan Paul⁴, Klemen Strle⁵, John A Branda⁶, Allen C Steere⁷, Douglas A Lauffenburger³, Galit Alter^{1

8}

Affiliations

¹ Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
² Brigham and Women's Hospital, Division of Infectious Diseases, Boston, MA 02115, USA.
³ Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
⁴ Marks Group, Department of Systems Biology, Harvard Medical School, Boston, MA, USA.
⁵ Tufts University School of Medicine Boston, Boston, MA, USA.
⁶ Department of Pathology, Massachusetts General Hospital, Boston, MA, USA.
⁷ Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
⁸ Moderna Therapeutics Inc., Cambridge, MA 02139, USA.

Abstract

Lyme arthritis, caused by the spirochete Borrelia burgdorferi, is the most common feature of late disseminated Lyme disease in the United States. While most Lyme arthritis resolves with antibiotics, termed "antibiotic-responsive", some individuals develop progressive synovitis despite antibiotic therapy, called "antibiotic-refractory" Lyme arthritis (LA). The primary drivers behind antibiotic-refractory arthritis remain incompletely understood. We performed a matched, cross-compartmental comparison of antibody profiles from blood and joint fluid of individuals with antibiotic-responsive (n = 11) or antibiotic-refractory LA (n = 31). While serum antibody profiles poorly discriminated responsive from refractory patients, a discrete profile of B.burgdorferi-specific antibodies in joint fluid discriminated antibiotic-responsive from refractory LA. Cross-compartmental comparison of antibody glycosylation, IgA1, and antibody-dependent complement deposition (ADCD) revealed more poorly coordinated humoral responses and increased ADCD in refractory disease. These data reveal B.burgdorferi-specific serological markers that may support early stratification and clinical management, and point to antibody-dependent complement activation as a key mechanism underlying persistent disease.

Keywords: Health sciences; Immunology; Microbiology.

Abstract

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