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Abstract Number: 2918

The Clinical Relevance of Common ANA Patterns in Systemic Sclerosis

Ashraf Raslan1, Clifford Stermer2 and Vivien Hsu3, 1Medicine, Rutgers-RWJ Medical School, Jersey City, NJ, 2Medicine, Rutgers-RWJMS, New York, NY, 3Rheumatology, RWJ Med Schl Scleroderma Prog, New Brunswick, NJ

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: ANA, antibodies and systemic sclerosis

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Session Information

Date: Tuesday, November 15, 2016

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

Session Type: ACR Poster Session C

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

Background/Purpose: Antinuclear antibody (ANA) test is positive in nearly 95% of patients with systemic sclerosis (SSc) [1]. We aim to identify the clinical relevance of common ANA patterns in SSc, of which there are only few published studies [2][3].

Methods: We evaluated 186 outpatients who met criteria for SSc [4] and were seen between 2010 and 2015. We collected pertinent clinical information, including ANA patterns (Homogeneous (H-ANA), speckled (S-ANA), nucleolar (N-ANA), centromere (C-ANA), and mixed [3]) performed by Indirect Immunofluorescence (IIF) and SSc auto-antibodies: RNA Polymerase III (POL3), Anti-topoisomerase I (anti-topo I), U-1 RNP, and Anti-Centromere (ACA).

Results: ANA was positive in 92% of patients (n=171) with the following patterns: H-ANA 27%, S-ANA 26%, N-ANA 12%, C-ANA 20% and mixed 14% (homogeneous & speckled 3%, homogeneous & nucleolar 5%, speckled & nucleolar 4%, speckled & centromere 1% and nucleolar & centromere 1%).   H-ANA was strongly associated with both anti-topo I (OR 24, CI 10.3-55.8) and diffuse cutaneous systemic sclerosis (dcSSc) (OR 5.5, CI 2.4-12.6). In addition, H-ANA was significantly associated with later age of disease onset, acro-osteolysis, hand contractures, interstitial lung disease (ILD), and lower forced vital capacity (FVC) and diffusion capacity of the lung for carbon monoxide (DLCO). S-ANA was strongly associated with POL 3 (OR 11.4, CI 4.4-29.9), U-1RNP (OR 7.3, CI 3-17.8), and tendon friction rubs (TFRs) (OR 2.8, CI1.3-5.9).   C-ANA was strongly associated with limited cutaneous systemic sclerosis (lsSSc) (OR 71, CI 9.4-533), and strongly protective against myopathy (OR 0.1, CI 0.01-0.8), TFRs (p=0.0002), hand contractures (OR 0.2, CI 0.08-0.7), and ILD (OR 0.3, CI 0.1-0.7). These patients had higher %FVC (p<0.0001) and %DLCO (p=0.006).  None of the SSc auto-antibodies were associated with the nucleolar pattern.

Conclusion: ANA patterns may be useful in predicting specific SSc auto-antibodies and clinical features. Larger studies could confirm our findings and help further understand the clinical significance of these ANA patterns in SSc. References:

1-     Bernstein et al. Clin Exp Imm. 1982; 48:43

2-     Hesselstrand et al. Rheumatology 2003; 42:534

3-     Sulli et al. J.Rheum. 2013;40:5

4-     Hoogen et al. Ann Rheum Dis. 2013; 72:1747 & Arthritis Rheum.  2013;65: 2737

 

  Table-1 Patient Demographics and Systemic Sclerosis subtypes in relation to ANA patterns
    ANA Positive n=171 (92%) ANA pattern by Indirect Immunofluorescence ANA Negative n=15(8%)
  Homogenous n=47 (27%) Speckled  n=45 (26%) Centromere n=34(20%) Nucleolar n=21(12%) Mixed n=24(14%)
    Mean (SD) or Col% Mean(SD) or Col% Mean(SD) or Col% Mean(SD) or Col% Mean(SD) or Col% Mean(SD) or Col% Mean(SD) or Col%
Age (years) 58.4(13) 59.7(11) 56(13) 62.4 (14.2) 55(11.8) 57.4(14.8) 62.4(13)
Female                                   Male 145(85%) 26(15%) 38(81%) 9(19%) 39(87%) 6(13%) 32(94%) 2(6%) 15(71%) 6(29%) 21(88%)  3(12%) 12(80%)  3(20%
Caucasian                   AA                                        Other 114(67%) 20(12%) 36(21%) 31(66%) 7(15%) 9(19%) 31(69%) 7(16%) 7(16%) 25(76%) 0(0%) 8(24%) 12(57%) 3(14%) 6(29%) 15(63%) 3(12%) 6(25%) 12(80%) 1(7%) 2(13%)
Hispanic                   Non-Hispanic 13(8%) 157(92%) 1(2%) 46(98%) 1(2%) 44(98%) 4(12%) 29(88%) 2(10%) 19(10%) 5(21%) 19(79%) 1(7%) 14(93%)
SSc type                 Diffuse Limited 94(55%) 76(45%) 39(83%)a 8(17%) p<0.0001 26(59%) 18(41%) 1(3%) 33(97%)b p<0.0001 13(62%) 8(38%) 15(63%) 9(37%) 10(67%) 5(33%)
Age at SSc Onset (year)* 44.7(12.8) 48.3(10.3) p=0.004 44.4(12.4) 44(13.2) 42(12.9) 41.6(16.6) 48(11.7)
Overlap w/ RA        Yes         No 38(22%) 131(78%) 12(26%) 34(74%) 14(31%) 31(69%) 5(15%) 29(85%) 4(19%) 17(81%) 3(12%) 21(88%) 3(20%) 12(80%)
Overlap w/Myositis                Yes         No 31(19%) 136(81%) 9(20%) 37(80%) 13(29%) 32(71%) 1(3%)c 32(97%) p=0.008 5(24%) 16(76%) 4(17%) 19(83%) 4(29%) 10(71%)

 a-OR=5.5, CI(2.4-12.6)       b-OR=71, CI(9.4-533)       c-OR=0.1, CI(0.01-0.8)     *From non-RaynaudÕs symptoms  SSc: systemic sclerosis; dcSSc: diffuse cutaneous systemic sclerosis; lcSSc: limited cutaneous systemic sclerosis; RA: rheumatoid arthritis

 

  Table-2: Systemic Sclerosis-specific auto-antibodies in relation to ANA patterns
    ANA Positive n=171 (92%) ANA pattern by Indirect Immunofluorescence ANA Negative n=15 (8%)
  Homogenous n=47 (27%) Speckled  n=45 (26%) Centromere n=34 (20%) Nucleolar n=21(12%) Mixed n=24 (14%)
    Mean (SD) or Col% Mean (SD) or Col% Mean (SD) or Col% Mean (SD) or Col% Mean (SD) or Col% Mean (SD) or Col% Mean (SD) or Col%
Anti-topo I          Positive Negative 50(29%) 120(71%) 35(74%) 12(26%) p<0.0001a 4(9%) 41(91%) 0(0%) 33(100%) 0(0%) 21(100%) p=0.003 11(46%) 13(54%) 0(0%) 15(100%) p=0.01
RNA-polymerase III           Positive Negative 23(16%) 122(84%) 4(10%) 38(90%) 17(45%) 21(55%) p<0.0001b 0(0%) 28(100%) 0(0%) 17(100%) p=0.05 2(12%) 15(88%) 2(14%) 12(86%)
Anti-Centromere     Positive Negative 42(25%) 127(75%) 0(0%) 46(100%) p<0.0001 4(9%) 40(91%) p=0.01 34(100%) 0(0%) p<0.0001 0(0%) 21(100%) p=0.003 4(21%) 15(79%) 0(0%) 15(100%) p=0.02
Anti-U-1 RNP             Positive Negative 26(16%) 141(84%) 3(7%) 42(93%) 16(36%) 28(64%) p<0.0001c 2(6%) 31(94%) 1(5%) 20(95%) 4(17%) 20(83%) 0(0%) 15(100%)

a-OR=24, CI(10.3-55.8)       b-OR=11.4, CI(4.4-29.9)       c-OR=7.3, CI(3-17.8) Anti-topo I: anti-topoisomerase I or Scl70  

 

  Table-3 Systemic Sclerosis clinical features in relation to ANA patterns  
    ANA Positive n=171 (92%) ANA pattern by Indirect Immunofluorescence ANA Negative n=15 (8%)
  Homogenous n=47 (27%) Speckled  n=45 (26%) Centromere n=34 (20%) Nucleolar n=21(12%) Mixed n=24 (14%)
    Mean (SD) or Col% Mean (SD) or Col% Mean (SD) or Col% Mean (SD) or Col% Mean (SD) or Col% Mean (SD) or Col% Mean (SD) or Col%
 Digital ulcers*      Yes           No 91(54%) 77(46%) 28(60%) 19(40%) 22(49%) 23(51%) 24(71%) 10(29%) 7(37%) 12(63%) 10(43%) 13(57%) 5(33%) 10(67%)
TFRs*   Yes           No 42(29%) 103(71%) 14(34%) 27(66%) 18(44%) 23(56%) p=0.007 0(0%) 30(100%) p=0.0002 5(31%) 11(69%) 5(29%) 12(71%) 2(14%) 12(86%)
Synovitis*            Yes           No 44(28%) 111(72%) 15(36%) 27(64%) 17(40%) 26(60%) 5(16%) 27(84%) 4(22%) 14(78%) 3(14%) 18(86%) 3(20%) 12(80%)
Acro-osteolysis**      Yes           No 35(24%) 112(76%) 15(38%) 25(62%) p=0.04 4(10%) 35(90%) 4(14%) 25(86%) 3(17%) 15(83%) 9(43%) 12(57%) 5(42%) 7(58%)
Calcinosis**             Yes           No 69(48%) 76(52%) 18(45%) 22(55%) 15(38%) 24(62%) 16(55%) 13(45%) 8(47%) 9(53%) 12(60%)  8(40%) 6(50%) 6(50%)
Hand Contractures*                        Yes           No 54(34%) 104(66%) 20(47%) 23(53%) p=0.03 15(36%) 27(64%) 4(13%) 27(87%) p=0.008 5(25%) 15(75%) 10(45%) 12(55%) 3(23%) 10(77%)
ILD ***                         Yes            No 101(68%)  47(32%) 39(83%)  8(17%) p=0.01 27(68%) 13(32%) 10(43%) 13(57%) p=0.005 13(72%)  5(28%) 12(60%)  8(40%) 10(71%)  4(29%)
FVC (%)   81.6%(20) 71.9%(17) p=0.02 83.1%(16.8) 97.2%(18.1) p<0.0001 72.8%(19.4) 82.6%(21.8) 71.6%(26.3)
DLCO (%) 64.3%(23.2) 55.2%(20.4) p=0.05 65.5%(21.5) 69.4%(20.8) p=0.006 66.3%(29.9) 70.5%(24.2) 48.5%(24.6)
Current mRSS* (SD) 4(6.6) 5.2(7.4) 4.2 (6.3) 2.2(2.7) 3.3(8.0) 4.4(7.8) 2.1(4.4)

*Documented on physical exam    **Documented by hand x-rays    ***Document by high resolution CT chest TFRs: tendon friction rubs; ILD: interstitial lung disease; FVC: forced vital capacity; DLCO: diffusion capacity of the lung for carbon monoxide mRSS: modified Rodnan skin score  


Disclosure: A. Raslan, None; C. Stermer, None; V. Hsu, None.

To cite this abstract in AMA style:

Raslan A, Stermer C, Hsu V. The Clinical Relevance of Common ANA Patterns in Systemic Sclerosis [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/the-clinical-relevance-of-common-ana-patterns-in-systemic-sclerosis/. Accessed .
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