Clinical Associations of Anti-Eukaryotic Initiation Factor 2B (anti-eIF2B) Antibodies in a Large Cohort of Patients with Anti-Nuclear Antibody Negative Systemic Sclerosis

John Pauling^1,2, Hui Lu¹, Zoe Betteridge^1,2, Gloria Salazar³, Shervin Assassi³, Maureen D Mayes³ and Neil J. McHugh^1,4, ¹Department of Pharmacy and Pharmacology, University of Bath, Bath, United Kingdom, ²Department of Rheumatology, Royal National Hospital for Rheumatic Diseases, Bath, United Kingdom, ³Rheumatology, University of Texas Health Science Center at Houston, Houston, TX, ⁴Rheumatology, Royal National Hospital for Rheumatic Diseases, Bath, United Kingdom

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: autoantibodies, Diagnostic Tests, interstitial lung disease and systemic sclerosis

Session Information

Date: Sunday, November 13, 2016

Title: Systemic Sclerosis, Fibrosing Syndromes, and Raynaud's – Clinical Aspects and Therapeutics - Poster I

Session Type: ACR Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose: Autoantibodies can be characterized in up to 95% of patients with systemic sclerosis (SSc) and provide enormous diagnostic and prognostic value in the clinical setting. We have recently identified a novel autoantibody in patients with SSc targeting Eukaryotic Initiation Factor 2B (anti-eIF2B). Earlier work identified an association with diffuse cutaneous systemic sclerosis (dcSSc) and interstitial lung disease (SSc-ILD), although the majority of samples had originated from a large tertiary referral respiratory unit managing patients with SSc-ILD. Anti-eIF2B positive sera has a cytoplasmic staining pattern on indirect immunofluorescence (IIF), but anti-nuclear antibody (ANA) staining is negative. The objectives of this study were to explore the prevalence and clinical associations of anti-eIF2B antibodies in ANA-negative samples obtained from a large US prospective study of SSc.

Methods: ANA-negative samples from the Scleroderma Family Registry and DNA Repository were tested by routine serological techniques followed by radiolabelled protein immunoprecipitation (IPP). Sera that immunoprecipitated a 30kDa band (consistent with anti-eIF2) underwent immunodepletion studies to confirm antigen specificity for eIF2B. The clinical phenotype of patients carrying anti-eIF2 was assessed.

Results: Of the 128 ANA-negative samples, a 30kDA band was identified on IPP in 10 samples (7.8%). Immunodepletion studies confirmed eIF2B as the antigen target in 9 samples. No other SSc-specific autoantibodies were identified in these 9 samples (suggesting mutual exclusivity). The clinical features of anti-eIF2B positive patients are presented (Table). All patients had Raynaud’s phenomenon (9/9, 100%). The majority of patients had dcSSc (8/9, 89%) although the mean modified Rodnan Skin Score (documented 7/9, 78%) was only 17.7. All patients with previous chest imaging (7/9, 78%) had radiographic evidence of SSc-ILD; either on computed tomography (6/6, 100%) and/or plain radiograph (4/4, 100%). Pulmonary function tests (documented in 7/9, 78%) revealed a mean FVC of 63.4% predicted and mean DLco of 64.3% predicted. The prevalence of digital ulcers and gastro-esophageal reflux disease was low (2/9, 22% for each). No patients had evidence of pulmonary arterial hypertension on echocardiography or right heart catheterization (when reported).

Conclusion: Anti-eIF2B is a novel, rare (estimated total prevalence in SSc ~1%) and mutually exclusive cytoplasmic autoantibody identified in approximately 7% of ANA-negative samples of patients with SSc. Our findings would support the previously reported clinical association of anti-eIF2B autoantibodies with dcSSc and SSc-ILD in a larger and more representative SSc patient population. Table. Clinical phenotype and outcome of pulmonary investigations of anti-eIF2B positive SSc patients * na, not available

	Ethnicity	Disease subset	Modified Rodnan skin score	FVC % predicted	DLco % predicted	SSc-ILD on CXR	SSc-ILD on CT
Patient 1	Non-hispanic white	Diffuse	na	84	86	Yes	na
Patient 2	Non-hispanic white	Diffuse	34	68	64	na	Yes
Patient 3	Non-hispanic white	Diffuse	18	na	na	Yes	na
Patient 4	Non-hispanic white	Diffuse	11	66	62	na	Yes
Patient 5	Non-hispanic white	Limited	15	42	67	Yes	Yes
Patient 6	Non-hispanic white	Diffuse	11	na	na	No	na
Patient 7	Non-hispanic white	Diffuse	12	79	79	na	Yes
Patient 8	Non-hispanic white	Diffuse	na	56	28	na	na
Patient 9	Black	Diffuse	23	49	na	Yes	Yes

Disclosure: J. Pauling, None; H. Lu, None; Z. Betteridge, None; G. Salazar, None; S. Assassi, None; M. D. Mayes, None; N. J. McHugh, None.

To cite this abstract in AMA style:

Pauling J, Lu H, Betteridge Z, Salazar G, Assassi S, Mayes MD, McHugh NJ. Clinical Associations of Anti-Eukaryotic Initiation Factor 2B (anti-eIF2B) Antibodies in a Large Cohort of Patients with Anti-Nuclear Antibody Negative Systemic Sclerosis [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/clinical-associations-of-anti-eukaryotic-initiation-factor-2b-anti-eif2b-antibodies-in-a-large-cohort-of-patients-with-anti-nuclear-antibody-negative-systemic-sclerosis/. Accessed .

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