Lacrimal and salivary immunoglobulins in Sjögren's syndrome

Journal of Autoimmunity (1989) 2,509-513

Lacrimal and Salivary Immunoglobulins in S jiigren’s Syndrome

Bernard Amor and Andre Kahan Department

ofRheumatology,

Hdpital Cochin, Renk Descartes

University,

75674 Paris Cedex 14, France The diagnosis of Sjiigren’s syndrome is sometimes difficult. We have previously demonstrated the diagnostic value of salivary immunoglobulins IgG and IgM in Sjiigren’s syndrome. In the present study, we assessed both lacrimal immunoglobulins (1 lg) and salivary lg (s lg) in Sjbgren’s syndrome. We studied 112 patients: 71 had rheumatoid arthritis (57 sero positive), 19 had connective tissue diseases or vasculitis (six SjSgren’s syndrome alone, six systemic sclerosis, three mixed connective tissue diseases, three polyarteritis, one relapsing polychondrltis), and 22 patients had other inflammatory, metabolic or degenerative joint diseases. Lacrimal lg and salivary lg were assessed by double immunodiffusion with antisera specific for IgG, IgM and IgA. Each lg class was scored on a scale ranging from 0 to 3 plus without knowledge of the patient’s diagnosis. The results of factorial analysis demonstrated a strong relationship between xerophtalmia, positive Schirmer’s test, s IgG, s IgM, 1 IgG, and 1 IgM in patients with seropositive rheumatoid arthritis or other connective tissue diseases. Analysis of Individual parameters showed a significant relationship between 1 IgG and ocular complaints (P
Lacrimal

and salivary

immunoglobulins

in Sjiigren’s

syndrome

SjGgren’s syndrome is a chronic inflammatory autoimmune disorder, characterized by the association of keratoconjunctivitis sicca and xerostomia, with or without a Correspondence to: Professeur B. Amor, Clinique de Rhumatologie, faubourg Saint Jacques, 75674 Paris Cedex 14, France.

Hbpital Cochin, 27, rue du

509 0896-8411/89/040509+04S03.00/0

0 1989 Academic Press Limited

510

B. Amor and A. Kahan

connective tissue disease [ 11. In Sjogren’s syndrome both the major and the minor salivary glands, as well as the lacrimal glands, are infiltrated by lymphoid cells [2,3] with associated secretory tissue destruction. Previous studies [3, 41 demonstrated that the lymphoid cells infiltrating the labial salivary glands in Sjdgren’s syndrome synthesized in vitro large amounts of immunoglobulins, especially IgG and IgM. It seemed of interest, therefore, to assess in vivo lacrimal and salivary immunoglobulins in patients with Sjogren’s syndrome. Our investigations of the lacrimal and salivary immunoglobulins are reported here, based upon three studies of patients with Sjogren’s syndrome, with or without associated connective tissue disease, and control subjects. The first study [5] assessed the salivary immunoglobulins in patients with rheumatoid arthritis and control subjects. The second study compared the salivary immunoglobulins in patients with Sjogren’s syndrome alone and in patients with Sjogren’s syndrome and rheumatoid arthritis. A third study assessed both lacrimal and salivary immunoglobulins in patients with Sjogren’s syndrome and control subjects. Patients and methods Patients (A) First study (5) A total of 74 adult patients underwent salivary immunoglobulins evaluation; 36 patients had rheumatoid arthritis and 10 an autoimmune disease possibly associated with Sjiigren’s syndrome; patients with degenerative joint disease and healthy subjects served as controls. (B) Second study Seventy-two patients with Sjogren’s syndrome were studied. Thirty patients had Sjogren’s syndrome alone and 42 had Sjogren’s syndrome and rheumatoid arthritis (30 patients had positive latex or Waaler-Rose tests). There were 64 females and eight males. The mean ( f SD) age was 55.9 + 13.1 years and the mean disease duration was 8.3 &-8.1 years. (C) Third study One hundred and twelve patients were studied. There were 90 females and 22 males. Seventy-one patients had rheumatoid arthritis (57 seropositive), 19 had connective tissue disease or vasculitis (six had Sjbgren’s syndrome alone, six systemic sclerosis, three mixed connective tissue disease, three polyarteritis, one relapsing polychondritis), and 22 had other inflammatory, metabolic, or degenerative joint diseases. Lacrimal and salivary immunoglobulins were also assessed to 10 healthy control subjects. Methods Saliva was collected without stimulation whereas lacrimal secretion (study no. 3) was obtained with or without stimulation. Salivary and lacrimal secretions were stored at - 20°C until use. For rapid screening, salivary and lacrimal immunoglobulins were

Lacrimal and salivary immunoglobulins

in S jiigren’s syndrome

5 11

scored on a scale ranging from 0 to 3+ by double immunodiffusion in agar plates using 7 1.11 of saliva (or tears) and respectively 5 ul, 4 ~1, and 3 l.tl of monospecific goat anti-human IgA, IgG, and IgM antisera after 4 h incubation at 37°C. Quantitative determination used radial immunodiffusion. Serum standards were used for salivary and lacrimal immunoglobulin determinations. Results (A) First study: salivary immunoglobulins in Sjogren’s syndrome and rheumatoid arthritis Salivary IgA were detected in all patients and control subjects, whereas salivary IgG were found in 42% patients with rheumatoid arthritis and 4Ob control subjects. Salivary IgM were observed in 1496 patients with rheumatoid arthritis and in Ooo controls. A significant relationship was found between the presence of salivary IgG and the existence of sicca syndrome (P
as well as lacrimal glands, are infiltrated with lymphoid cells [ l-3,6]. Talal et al. [3] and Anderson et al. [4] demonstrated

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Figure 1. Lacrimal and salivary immunoglobulins in SjGgren’s syndrome. A significant relationship was found between lacrimal IgG (1 IgG), lacrimal IgM (I IgM), salivary IgG (s IgG), salivary IgM (s IgM), xerophtahnia, and positive Schirmer’s test (factorial analysis).

that labial salivary gland tissue from patients with Sjogren’s syndrome were producing in vitro significantly greater quantities of IgG, IgM and IgA than control subjects. Synthesis of IgGand IgM correlated with the degree of lymphoid infiltration but not with serum immunoglobulin concentration [3]. In normal subjects, IgA is the major immunoglobulin produced by salivary gland tissue [7] and the presence of salivary IgG or IgM is quite rare. However, salivary IgG or IgM have been detected in patients with mouth or dental infections, multiple myeloma, Waldenstrom’s macroglobulinemia, or IgA deficiency [5,7,8]. In contrast, the results of the present studies demonstrate that salivary IgG or IgM are found in approximately half of the patients with Sjogren’s syndrome. The frequency of salivary IgG or IgM was slightly higher in patients with Sjogren’s syndrome alone than in those with Sjdgren’s syndrome and rheumatoid arthritis, but the difference did not reach statistical significance. Finally, a significant relationship was found between lacrimal IgG or IgM and the sicca syndrome. These results suggest that the detection of lacrimal and salivary IgG or IgM may be a useful diagnostic test in Sjogren’s syndrome. Lacrimal secretions, however, are often difficult to obtain in patients with severe Sjogren’s syndrome. In contrast, for salivary immunoglobulins, the test is simple to perform and involves minimal patient discomfort. Long-term studies are warranted to determine whether salivary or lacrimal IgG or IgM are useful markers to evaluate disease severity and response to treatment.

Lacrimal and salivary immunoglobulins

in S jiigren’s syndrome

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References 1. Cummings,N. A., G. L. Schall,R. Asofsky, L. G. Anderson, andN. Talal. 1971. Sjogren’s syndrome: newer aspects of research, diagnosis, and therapy. Ann. Intern. Med. 75: 937-950 2. Chisholm, D. M. and D. K. Mason. 1968. Labial salivary gland biopsy in Sjogren’s disease. J. Clin. Pathol. 21: 656-660 3. Talal, N., R. Asofsky, and P. Lightbody. 1970. Immunoglobulin synthesis by salivary gland lymphoid cells in Sjogren’s syndrome. J. Clin. Invest. 49: 49-54 4. Anderson, L. G., N. A. Cummings, R. Asofsky, M. B. Hylton, T. M. Tarpley, T. B. Tomasi, R. 0. Wolf, G. L. Schall, and N. Talal. 1972. Salivary gland immunoglobulin and rheumatoid factor synthesis in Sjogren’s syndrome. Natural history and response to treatment. Am. J. Med. 53: 456-463 5. Amor, B., I’. S. Mach, R. Ghozlan, and F. Delbarre. 1977. La determination des immunoglobulines salivaires. Son inter&t dam le diagnostic du syndrome de Gougerot Sjogren. Rev. Rhum. Mal. Osteoartic. 44: 491-496. 6. Bunim, J. J., W. W. Buchanan, P. T. Wertlake, L. Sokoloff, K. J. Block, J. S. Beck, and F. P. Alepa. 1964. Clinical, pathological, and serological studies in Sjogren’s syndrome. Ann. Intern. Med. 61: 509-530. 7. Tomasi, T. B. 1972. Secretory immunoglobulins. N. EngZ.J. Med. 287: 500-506 8. Anderson, L. G. and N. Talal. 1972. The spectrum of benign to malignant lymphoproliferation in Sjogren’s syndrome. Clin. Exp. Zmmunol. 10: 199-221