Decrease in immunoglobulin free light chains in patients with rheumatoid arthritis upon rituximab (anti-CD20) treatment correlates with decrease in disease activity

Kormelink, Tom Groot; Tekstra, Janneke; Thurlings, Rogier M.; Boumans, Mjh; Vos, Koen; Tak, Paul P.; Bijlsma, J. W. J.; Lafeber, F.P.; Redegeld, Frank A.; Roon, J. A. G. Van

doi:10.1136/ard.2009.126441

Cited by 65 publications

(40 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…β2-microglobulin levels show a 'delayed' drop at 16 weeks after treatment [8,12], which was not seen at 6 or 12 weeks after rituximab treatment [8,11]. Serum immunoglobulin free light chains (FLCs) are also affected by rituximab and decrease significantly from week 5 up to week 48 after treatment (unpublished data), in line with findings in RA [19]. Both β2-microglobulin and FLC baseline levels in serum of pSS patients are positively correlated to ESSDAI scores [20], suggesting that there is a link between the degree of B cell activation and systemic disease activity.…”

Section: Introductionsupporting

confidence: 71%

The value of rituximab treatment in primary Sjögren's syndrome

Verstappen

Nimwegen

Vissink

et al. 2017

Clinical Immunology

View full text Add to dashboard Cite

Section: Introductionsupporting

confidence: 71%

The value of rituximab treatment in primary Sjögren's syndrome

Verstappen

Nimwegen

Vissink

et al. 2017

Clinical Immunology

View full text Add to dashboard Cite

“…Further, when Ab LC are multiply displayed on the nanovesicle surface, the overall avidity for Ag likely increases, particularly in this hapten system where there is only one Ag determinant. Free Ig LC previously have been implicated in a variety of immune and allergic inflammatory diseases 40-43 and may be one mechanism for the beneficial effect of anti-CD20 B cell therapy with Rituximab 44,45 . Effects of Ab LC in diverse responses first were ascribed to binding and activating mast cells 11,30,40-43,46 , but binding of Ab LC to human T cells, B cells and monocytes has been recently demonstrated 47 .…”

Section: Discussionmentioning

confidence: 99%

Antigen-specific, antibody-coated, exosome-like nanovesicles deliver suppressor T-cell microRNA-150 to effector T cells to inhibit contact sensitivity

Bryniarski

Ptak

Jayakumar

et al. 2013

Journal of Allergy and Clinical Immunology

185

352

View full text Add to dashboard Cite

Background T cell tolerance of allergic cutaneous contact sensitivity (CS) induced in mice by high doses of reactive hapten is mediated by suppressor cells that release antigen-specific suppressive nanovesicles. Objective To determine the mechanism(s) of immune suppression mediated by the nanovesicles. Methods T cell tolerance was induced by i.v. injections of hapten conjugated to self antigens of syngeneic erythrocytes and subsequent contact immunization with the same hapten. Lymph node and spleen cells from tolerized or control donors were harvested and cultured to produce a supernatant containing suppressive nanovesicles that were isolated for testing in active and adoptive cell transfer models of CS. Results Tolerance was shown due to exosome-like nanovesicles in the supernatant of CD8+ suppressor T cells that were not Treg. Antigen specificity of the suppressive nanovesicles was conferred by a surface coat of antibody light chains, or possibly whole antibody, allowing targeted delivery of selected inhibitory miRNA-150 to CS effector T cells. Nanovesicles also inhibited CS in actively sensitized mice after systemic injection at the peak of the responses. The role of antibody and miRNA-150 was established by tolerizing either panimmunoglobulin deficient JH-/- or miRNA-150-/- mice that produced non-suppressive nanovesicles. These nanovesicles could be made suppressive by adding antigen-specific antibody light chains or miRNA-150, respectively. Conclusions This is the first example of T cell regulation via systemic transit of exosome-like nanovesicles delivering a chosen inhibitory miRNA to target effector T cells in an antigen-specific manner by a surface coating of antibody light chains.

show abstract

“…A second course of RTX may achieve a clinical response even in patients who did not respond to the first course; this may relate to the extent of peripheral B cell depletion (category C evidence90). …”

Section: Rituximabmentioning

confidence: 99%