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Abstract Number: 1516

Evidence of Labial Salivary Gland Epithelial Cell Activation from Patients with Rheumatoid Arthritis and Sicca Symptomatology

George Fragoulis1, James Reilly1, Shauna Kerr1, Iain B McInnes2 and Haralampos M. Moutsopoulos3, 1Institute of Infection, Immunity and Inflammation, College of Medicine, Veterinary Medicine and Life Sciences, University of Glasgow, Glasgow, United Kingdom, 2University of Glasgow, Glasgow, Great Britain, 3Pathophysiology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: rheumatoid arthritis (RA) and salivary gland, SICCA, Sjogren's syndrome

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Session Information

Date: Monday, November 14, 2016

Title: Rheumatoid Arthritis – Clinical Aspects - Poster II: Co-morbidities and Complications

Session Type: ACR Poster Session B

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

Background/Purpose: In primary Sjögren’s syndrome (pSS), labial minor salivary gland epithelial cells (LMSGEC) inappropriately express various molecules, including B7, HLA-DR, ICAM, as assessed previously by in-situ and in-vitro studies, indicating an epithelial cell activation. Sicca symptomatology is encountered in around 30% of rheumatoid arthritis patients (RA-sicca). We previously showed that RA-sicca labial minor salivary gland (LMSG) lesions differ from those observed in pSS, primarily by displaying higher frequency of antigen presenting cells (APCs) [1]. Also, in a subgroup of RA-sicca patients, LMSGECs were found to express the B7 molecule. Interestingly patients exhibiting B7-positive LMSGECs had distinct histopathological and clinicoserological characteristics resembling those observed in pSS. We sought to further investigate if there is, indeed, evidence of a pSS-like epithelial activation in this subgroup of RA-sicca patients.

Methods: Serial sections of LMSGs from 32 RA patients (2010 ACR criteria) with sicca symptoms were evaluated with immunohistochemistry for the presence of total T cells, helper and cytotoxic T cell subpopulations, B cells, macrophages (ΜΦ), interdigitating (iDC) and follicular dendritic cells (fDC) and for the expression of B7, HLA-DR and ICAM molecules. Stained cells and total mononuclear cells (MNC) were counted in the entire section. Counts were expressed as cell frequency (% of cell type/total infiltrating MNC numbers) and staining for activation markers was assessed on an arbitrary scale (0-1). Correlations between epithelial cell activation status and cell frequencies or clinicoserological features were performed.

Results: LMSGECs in 16/32 patients were triple (B7.1, HLA-DR, ICAM) positive while the rest were either single, double or triple negative. Triple positive patients versus the remaining ones had more severe LMSG lesions (focus score; Mann Whitney, p=0.05) and exhibited lower frequencies of MΦ, iDCs and fDCs (Table 1). No differences on clinicoserological features were observed among groups. Expression of the aforementioned molecules by primary cultured LMSGECs of the same patients will be confirmed by flow cytometry.

Conclusion: A distinct subgroup was identified within the RA-sicca patients. This is characterized by expression of activation markers by their LMSGECs and also by an immunohistopathological pattern resembling pSS rather than RA-sicca. In vitro studies of primary LMSGEC cultures will confirm if these cells are indeed activated in such patients. 1. GE Fragoulis, et al. Analysis of the cell populations composing the mononuclear cell infiltrates in the labial minor salivary glands from patients with rheumatoid arthritis and sicca syndrome. J Autoimmun. 2016 (In press)

Table 1: Epidemiological, clinicoserological and histopathological features. a. Kruskal-Wallis and chi-square test for continuous and categorical variables, respectively.

Patients characteristics

Triple negative

 N=3

Single positive

N=6

Double positive

N=7

Triple positive

N=16

p-valuea

Epidemiological

Age, median (range)

61 (56-68)

57 (41-64)

56 (44-64)

61 (32-69)

0.473

Sex female, N (%)

3 (100.0)

6 (100.0)

7 (100.0)

14 (87.5)

0.597

Total follow up, months (mean ± SD)

90.0 ± 81.2

55.1 ± 36.1

119.0 ± 63.2

71.9 ± 80.7

0.283

Criteria

Ocular dryness (subjective), N (%)

2 (66.6)

5 (83.3)

3 (42.9)

15 (93.8)

0.105

Oral dryness (subjective), N (%)

1 (33.3)

4 (66.6)

5 (71.4)

8 (50.0)

0.351

Tarpley score, median (range)

1 (0-1)

1 (0-2)

1 (0-3)

2 (0-3)

0.836

Focus score, (mean ± SD)

0.33 ± 0.42

1.08 ± 0.76

0.79 ± 1.12

2.39 ± 3.02

0.347

Laboratory

 

 

 

ANA positive, N (%)

2 (66.6)

5 (83.3)

4 (57.1)

13 (81.2)

0.206

Anti-Ro/SSA positive, N (%)

1 (33.3)

2 (33.3)

2 (28.6)

5 (31.2)

0.996

Anti-La/SSB positive, N (%)

0 (0.0)

0 (0.0)

0 (0.0)

0 (0.0)

1.000

RF positive, N (%)

3 (100.0)

5 (83.3)

4 (57.1)

13 (81.2)

0.700

Anti-CCP positive, N (%)

2 (66.6)

6 (100.0)

4 (57.1)

8 (50.0)

0.085

C3 (mg/dl), (mean ± SD)

111.0 ± 34.4

123.5 ± 18.7

121.8 ± 32.1

103.8 ± 19.8

0.413

C4 (mg/dl), (mean ± SD)

26.7 ± 3.8

23.0 ± 11.9

24.3 ± 7.2

20.3 ± 7.3

0.498

Clinical

 

 

 

Fatigue, N (%)

1 (33.3)

0 (0.0)

2 (28.6)

7 (43.8)

0.317

Raynaud’s phenomenon, N (%)

1 (33.3)

2 (33.3)

3 (42.9)

5 (31.3)

0.840

Morning stiffness N (%)

3 (100.)

5 (83.3)

6 (85.7)

12 (75.0)

0.339

Liver/renal/lung involvement, N (%)

0 (0.0)

0 (0.0)

1 (14.2)

2 (12.5)

0.735

Serositis, N (%)

0 (0.0)

0 (0.0)

0 (0.0)

1 (6.3)

0.823

Myositis, N (%)

0 (0.0)

0 (0.0)

1 (14.2)

0 (0.0)

0.215

Peripheral nerve involvement, N (%)

1 (33.3)

0 (0.0)

2 (28.6)

1 (6.3)

0.164

Purpura, N (%)

0 (0.0)

0 (0.0)

1 (14.2)

3 (18.8)

0.616

Salivary gland enlargement, N (%)

0 (0.0)

0 (0.0)

1 (14.2)

2 (12.5)

0.700

Lymphoma, N (%)

0 (0.0)

0 (0.0)

0 (0.0)

1 (6.3)

0.823

Histopathological

mean±SD

%CD20+ B cells

47.9 ± 15.0

45.1 ± 7.3

35.9 ± 7.1

45.9 ± 12.6

0.457

%CD3+ T cells

46.5 ± 16.2

39.7 ± 2.8

41.9 ± 6.3

44.8 ± 12.4

0.771

%CD4+ T cells

24.0 ± 12.1

19.3 ± 6.8

21.8 ± 7.6

28.1 ± 7.9

0.727

%CD8+ T cells

20.7 ± 5.4

18.9 ± 5.4

19.5 ± 4.2

16.8 ± 5.5

0.512

%CD68+ MΦs

2.8 ± 1.7

7.3 ± 2.3

8.1 ± 3.0

4.1 ± 2.0

0.009

%S100+ iDCs

1.1 ± 0.7

1.8 ± 1.0

3.5 ± 2.0

1.2 ± 1.1

0.02

%fascin+ fDCs

2.2 ± 0.8

4.5 ± 2.3

6.5 ± 1.5

3.2 ± 1.7

0.02


Disclosure: G. Fragoulis, None; J. Reilly, None; S. Kerr, None; I. B. McInnes, None; H. M. Moutsopoulos, None.

To cite this abstract in AMA style:

Fragoulis G, Reilly J, Kerr S, McInnes IB, Moutsopoulos HM. Evidence of Labial Salivary Gland Epithelial Cell Activation from Patients with Rheumatoid Arthritis and Sicca Symptomatology [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/evidence-of-labial-salivary-gland-epithelial-cell-activation-from-patients-with-rheumatoid-arthritis-and-sicca-symptomatology/. Accessed .
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