Involvement of B cells in non‐infectious uveitis

Abstract

Non-infectious uveitis—or intraocular inflammatory disease—causes substantial visual morbidity and reduced quality of life amongst affected individuals. To date, research of pathogenic mechanisms has largely been focused on processes involving T lymphocyte and/or myeloid leukocyte populations. Involvement of B lymphocytes has received relatively little attention. In contrast, B-cell pathobiology is a major field within general immunological research, and large clinical trials have showed that treatments targeting B cells are highly effective for multiple systemic inflammatory diseases. B cells, including the terminally differentiated plasma cell that produces antibody, are found in the human eye in different forms of non-infectious uveitis; in some cases, these cells outnumber other leukocyte subsets. Recent case reports and small case series suggest that B-cell blockade may be therapeutic for patients with non-infectious uveitis. As well as secretion of antibody, B cells may promote intraocular inflammation by presentation of antigen to T cells, production of multiple inflammatory cytokines and support of T-cell survival. B cells may also perform various immunomodulatory activities within the eye. This translational review summarizes the evidence for B-cell involvement in non-infectious uveitis, and considers the potential contributions of B cells to the development and control of the disease. Manipulations of B cells and/or their products are promising new approaches to the treatment of non-infectious uveitis.

Tubulointerstitial nephritis and uveitis

“…Therefore, it is not clear if mCRP is truly a specific antigen involved in ocular and renal disease, or if these findings represent an auto-antibody that develops to this acute phase reactant as a results of chronic inflammation as has been reported previously in lupus nephritis [47]. Understanding the role of humoral immunity in uveitis has become more important as we try to explain the success of rituximab, a B-cell depleting biologic therapy, on certain forms of recalcitrant uveitis [48,49]. A more thorough understanding of TINU pathogenesis may also uncover an important role for humoral immunity in other forms of uveitis.…”

Identification of unique proteins in vitreous fluid of patients with noninfectious uveitis

“…Unlike infectious uveitis, noninfectious or autoimmune uveitis may be associated with HLA-induced inflammation (Caspi 2006;Klaska & Forrester 2015). B cells may have important role to promote intraocular inflammation by T-cell activation following release of multiple cytokines (Smith et al 2016). Patients suffering from noninfectious uveitis largely exhibit innate immune responses towards immunologically privileged ocular antigens.…”

Intraocular chemotherapy for vitreoretinal lymphoma: A review

“…In targeting B lymphocytes, rituximab effects depletion of the B lymphocytes by multiple mechanisms that include antibody‐dependent cellular cytotoxicity, complement‐dependent cytotoxicity and lymphocyte apoptosis. The drug is used systemically in the treatment of a range of B lymphocyte‐mediated diseases: autoimmune diseases, including some forms of uveitis; and B‐cell lymphomas, including PCNSL . The first reported uses of intraocular rituximab therapy for VRL were in 2007, by Kitzmann et al from Mayo Clinic (Rochester, MN) and Ohgura et al from Osaka University Medical School (Osaka, Japan): a total of eight eyes of five patients were treated with up to four intravitreal injections of rituximab.…”