Presence of Antibodies Binding to Negative Elongation Factor E in Sarcoidosis

Abstract

Sarcoidosis is characterized by multiorgan involvement and granulomatous inflammation. Its origin is unknown and the potential role of autoimmunity has not been sufficiently determined. We investigated the presence of autoantibodies in sarcoidosis using protein array technology. The derivation cohort consisted of patients with sarcoidosis (n = 25) and controls including autoimmune disease and blood donors (n = 246). In addition, we tested a validation cohort including pulmonary sarcoidosis patients (n = 58) and healthy controls (n = 13). Initially, sera of three patients with sarcoidosis were screened using a protein array with 28.000 proteins against controls. Thereby we identified the Negative Elongation Factor E (NELF-E) as an autoantigen. With confirmatory Enzyme-linked Immunosorbent Assay (ELISA)testing, 29/82 patients (35%) with sarcoidosis had antibodies against NELF-E of the Immunoglobulin (Ig) G type, whereas 18/253 (7%) sera of the controls were positive for NELF-E. Clinically, there was an association of the frequency of NELF-E antibody detection with lung parenchymal involvement and corresponding x-ray types. NELF-E autoantibodies are associated with sarcoidosis and should be further investigated.

Management of Sarcoidosis, a Selection of Topical Items Updating

“…However, noteworthy preliminary unpublished data from the same group suggests that NELF-E auto-antibodies may develop because of a mimicry between a certain part of the amino acid sequence of NELF-E and Mycobacteroides abscessus or other bacteria. This noteworthy contribution from Baerlecken et al reinforces the discussion about the classification of sarcoidosis among the vast spectrum of immune or inflammatory systemic diseases, which has always been a puzzle—immune granulomatous disease (association of innate and adaptative immunity; activation and typical granulomas), auto-inflammatory disease (inflammasome activation) or auto-immune disease (humoral and/or immune recognition of autoantigens) [ 16 ]? Or, closer to reality, a polygenic auto-inflammatory disease with autoimmune features [ 9 , 22 ]?…”

“…This debate has been illustrated by the Mahévas et al study on the association of sarcoidosis and immune thrombocytopenia [ 15 ]. The report of auto-antibodies functional against Negative Elongation Factor E (NELF-E) in sarcoidosis by Baerlecken et al makes an additional significant contribution to the discussion of the “nature” of sarcoidosis [ 16 ]. J Grunewald and his team deserve the credit for demonstrating that auto-immunity, especially towards vimentin as an autoantigen, is a component of sarcoidosis as a disease [ 17 , 18 ].…”

“…Vimentin was identified as a major antigen in the Kveim test substance [ 19 ], and was detected in asteroid bodies of sarcoidosis granulomas [ 20 ]. Baerlecken et al identified in 35% of sarcoidosis (vs. 7% in controls, healthy patients or patients with auto-immune diseases) the Negative Elongation Factor E (NELF-E) as another auto-antigen [ 16 ]. Moreover, they found an association of the frequency of NELF-E antibody detection with lung parenchymal involvement.…”

Association between neurosarcoidosis with autonomic dysfunction and anti-ganglionic acetylcholine receptor antibodies

“…Patients with sarcoidosis frequently have higher titers of autoantibodies than healthy individuals [27][28][29]. Several autoantibodies, including anti-mitochondrial, anti-nuclear, anti-double stranded DNA, anti-citrullinated cyclic peptide, rheumatoid factor, antivimentin, and anti-negative elongation factor E, have been detected in sarcoidosis [27][28][29][30][31][32][33][34]. To the best of our knowledge, no previous study has reported anti-gAChR antibodies in sarcoidosis.…”