Rituximab treatment of the anti-synthetase syndrome—a retrospective case series

Abstract

This retrospective case series indicates a short-term beneficial effect of rituximab in ASS. Prospective, controlled studies are needed to validate this finding and further assess safety issues.

C-X-C Motif Chemokine 13 (CXCL13) Is a Prognostic Biomarker of Idiopathic Pulmonary Fibrosis

“…However, these nonspecific agents are similarly ineffectual as primary (or sole) therapy of numerous (if not all) other antibody-mediated lung diseases, including granulomatosis with polyangitis (Wegener's) (or antineutrophil cytoplasmic antibody-associated pulmonary vasculitides); Goodpasture syndrome; interstitial lung diseases (especially acute exacerbations) associated with polymyositis, scleroderma, and other conventional connective tissue diseases; or donor-specific antibodies in lung transplant recipients with chronic allograft rejection. Conversely, therapeutic modalities that deplete antibodies or target the B cells that produce these immunoglobulins often have beneficial clinical effects (25)(26)(27)(28)(29). A preliminary report indicates that autoantibody-targeted therapies may similarly benefit patients with Definitions of abbreviations: CXCL13 = C-X-C motif chemokine 13; DL CO = diffusing capacity of carbon monoxide; IPF = idiopathic pulmonary fibrosis.…”

“…These cumulative findings could ultimately influence incremental investigations and approaches to treatment of this morbid and heretofore inexorable lung disease. In addition to currently available regimens for treatment of antibody-mediated syndromes (25)(26)(27)(28)(29)48), the development of biologic response modifiers with specific actions at discrete, critical steps of pathologic B-cell response pathways is a very active area of ongoing research, and there is reason to believe that even more efficacious therapies will be available in the not-too-distant future (7,35,49). n…”

“…As an example, antibody-mediated lung diseases are resistant to treatment with nonspecific immunosuppressants (e.g., glucocorticoids), as is IPF, whereas approaches that physically remove antibodies, or target the B cells that produce these immunoglobulins, more often have favorable clinical effects (25)(26)(27)(28)(29). If B cells play an important role in IPF pathogenesis, analogous, more mechanistically focused treatment regimens might also benefit patients with this otherwise inexorable syndrome (30).…”

The Antisynthetase Syndrome

“…However, in our experience this regimen is insufficient in cases with acute and rapidly progressing ILD. Although based on retrospective case series, we recommend a combination of oral corticosteroids, cyclophosphamide and the anti-CD-20 monoclonal antibody rituximab as induction therapy in type I ASS (57). The efficacy of rituximab has also been reported in several case reports (58;59).…”

Aminoacyl-tRNA Synthetases in Idiopathic Inflammatory Myopathies: An Update on Immunopathogenic Significance, Clinical and Therapeutic Implications

“…Aggressive therapy such as intravenous immunoglobulins or newer biological are controversial, as there are no data to define firmly long-term disease outcomes in such conditions. Furthermore, advancing knowledge about the potential benefits of rituximab, an anti-CD20 monoclonal antibody, in life threatening antisynthetase syndrome provide conflicting data (Ball et al, 2010;Labirua & Lundberg, 2010;Sem et al, 2009;Vandenbroucke et al, 2009). An attractive therapeutic approach fundamentally based on antagonists of the targeted chemokine receptors has already been proposed, but not yet validated; the design of such intervention was suggested by the paradigm of chemokine receptor mediated cell migration triggered by autoantigens like aminoacyl-tRNA synthetases (Howard, 2006).…”