Biopsy Focus Score Research Articles

Ultra-high frequency ultrasonography (UHFUS)-guided minor salivary gland biopsy: A promising procedure to optimize labial salivary gland biopsy in Sjögren's syndrome.

Sjögren's syndrome (SS) is an autoimmune disease characterized by an inflammatory infiltrate of exocrine salivary and lachrymal glands. Diagnosis is complex, and minor salivary gland biopsy and subsequent focus score (FS) calculation appear of extreme importance in the diagnostic work-up of the disease. Ultra-high frequency ultrasonography (UHFUS) is a recently introduced diagnostic technique, which is gaining an increasingly important role in intraoral imaging. This study aims at exploring the usefulness of UHFUS for obtaining valuable labial salivary gland samples to assess the histopathological features of SS patients. Patients with clinical suspect of SS and eligible for minor salivary gland biopsy were enrolled. UHFUS scan of the lower lip was performed. Glandular echostructure was classified according to Outcome Measures in Rheumatology (OMERACT) scoring system. The glands to be sampled were selected on the basis of UHFUS evaluation and biopsied. The areas of the samples were recorded and compared with those obtained without UHFUS guidance. The correlation between UHFUS grade and labial gland FS was also assessed. The areas of the samples obtained with UHFUS guidance were significantly higher (7.25±3.98mm2 ) than those obtained by conventional procedures (5.79±3.49mm2 , P=.02). UHFUS correlated significantly with the salivary gland FS (r=.532, P=.001). UHFUS seems a promising tool in SS diagnostic algorithm, being able to provide a valuable support to the biopsy procedure. Further studies are mandatory to confirm the role of UHFUS in SS.

OP0042 THE TRANSCRIPTOME OF PAIRED MINOR AND MAJOR SALIVARY GLAND TISSUE IN PATIENTS WITH PRIMARY SJÖGREN’S SYNDROME: TWO OF A KIND?

Background:In patients with primary Sjögren’s syndrome (pSS), both minor and major salivary glands are targets of the disease. Infiltration of salivary glands by immune cells is characteristic for pSS. However, significant inter- and intra-individual variation exists in the size and composition of the infiltrates. Potential differences between minor and major salivary glands in immune cell presence and inflammatory pathway activation are unclear. This knowledge is essential for clinical trial design and precision therapy.Objectives:To compare the transcriptome of paired labial and parotid salivary gland tissue of patients with pSS and non-SS sicca controls.Methods:Thirty-nine pSS patients and 20 age- and sex-matched non-SS sicca controls, who participated in a prospective diagnostic cohort[1], were included. All pSS patients fulfilled 2016 ACR-EULAR criteria. RNA was isolated from formalin-fixed, paraffin-embedded labial and parotid gland tissue sections from the same individuals. Complementary DNA libraries were prepared and sequenced. Biopsies with evidence of sclerosing chronic sialoadenitis or mucosa-associated lymphoid tissue lymphoma were excluded in the current analysis. For differential gene expression analysis, patients were subdivided in four categories: I) non-SS sicca without lymphocytic infiltration, II) non-SS sicca with aspecific infiltration, III) pSS with negative biopsy (focus score<1), IV) pSS with positive biopsy (focus score≥1). For each differentially expressed gene (DEG), a false detection rate (FDR) was calculated. FDR<0.05 was considered significant.Results:Principal component analysis (PCA) showed that only pSS patients with a positive biopsy (group IV) could be separated from the non-SS sicca patients based on gene expression. When comparing the labial and parotid gland transcriptome, resp. 798 and 1461 DEGs (FDR-adjusted p-value<0.05, log2 fold change >1) were identified between groups I and IV. The top differentially regulated genes were mostly related to T and B cells.CXCL13, CCR6, MS4A1(CD20), FCRL4andDAZLwere among the genes with the highest positive fold change in both glands of biopsy-positive pSS patients. Overall, there was a moderate to strong correlation between fold changes in labial and parotid glands (R2=0.58, p-value<0.0001). Between biopsy-negative and biopsy-positive pSS (groups III and IV), 226 and 962 DEGs were identified for labial and parotid gland tissue, respectively. Interestingly, we could not identify DEGs between biopsy-negative pSS (group III) and non-SS sicca patients (group I).Conclusion:The transcriptome of labial and parotid gland tissue from pSS patients with a positive biopsy is overall comparable, while salivary gland tissue from biopsy-negative pSS patients shows a comparable gene expression profile to non-SS sicca controls. These results indicate that different treatment strategies may be necessary for biopsy-negative and biopsy-positive pSS patients.

Usefulness of rheumatoid factor as an immunological and prognostic marker in PSS patients

IntroductionThe rheumatoid factor (RF) is present in numerous autoimmune disorders, although its role in many of them remains a subject of research. The study assesses the role of RF as an immunological and prognostic factor in the primary Sjögren’s syndrome (pSS).MethodsSeventy-five pSS patients (mean age 50.03 ± 15.1), 65 (87%) females, and 10 (13%) males. WBC, CRP, RF, ESR, gammaglobulins, C4, C3 component of complement, cryoglobulins, ANA, anti-SS-A, and anti-SS-B antibodies were determined. The disease activity assessed with ESSDAI. Minor salivary gland biopsy (focus score and immunochemistry) was conducted. Results were analyzed with U Mann-Whitney (continuous variables) tests, correlations between quantitative variables assessed with the Spearman correlation coefficient with statistical significance set at p < 0.05. The approval of the Bioethics Committee was obtained.ResultsTwo subgroups I-RF(+) (61%) and II-RF(−) (39%) were established, with lower WBC (p = 0.012) and higher ESR (p = 0.016), gammaglobulin concentration (p = 0.007) in group I. Conjunctivitis sicca was more severe in group I. There was positive correlation between RF and lnANA (rho = 0.496), anti-SS-A, anti-SS-B antibodies (rho = 0.448; rho = 0.397 respectively). There was higher disease activity ESSDAI in group I than in group II (Me, 3.0 vs 2.0; p < 0.003). RF correlated negatively with WBC (rho = − 0.374). RF did not correlate with serum concentrations of BAFF, APRIL, CRP, and C3, C4 and with CD19+, CD3+, CD4+, CD 21+, and CD35+.ConclusionsRF should be considered as a prognostic, but not diagnostic, factor in patients with pSS, as it is associated with more severe disease course (sicca eye symptoms, ESSDAI) and parameters (production of gammaglobulins, ANA, anti SS-A, anti-SS-B autoantibodies) indicating increased B cell activity.

Lymphocytic focus score is positively related to airway and interstitial lung diseases in primary Sjögren's syndrome

Although high-resolution computed tomography (HRCT) is useful for the characterization of minute morphological changes in the lungs, no study has investigated risk factors for lung involvement detected by HRCT in patients with Sjögren's syndrome with or without respiratory symptoms. The aim of the current study was to investigate risk factors for lung involvement in patients with primary Sjögren's syndrome detected by HRCT, with a particular focus on airway and interstitial lung diseases. We performed a retrospective cohort study of patients with primary Sjögren's syndrome and investigated risk factors for lung involvement detected by HRCT. A total of 101 patients with primary Sjögren's syndrome with initial HRCT examinations were enrolled. Higher age, dry mouth, and higher labial gland biopsy focus scores (≥4) were risk factors for airway diseases (odds ratio [OR] 1.064 confidence interval [CI] 1.026-1.102, OR 8.795 CI 2.317-33.378 and OR 3.261 CI 1.100-9.675, respectively) in the multivariable analysis. Higher age, male sex, and higher labial gland biopsy focus scores (≥4) were risk factors for interstitial lung diseases (OR 1.078 CI 1.032-1.127, OR 12.178 CI 1.121-132.307 and OR 3.954 CI 1.423-10.987, respectively) in the multivariable analysis. The presence of anti-T-lymphotropic virus type 1 antibodies was significantly more common in patients with airway diseases. This study showed significant associations of labial gland biopsy focus scores and dry mouth with pulmonary manifestations in patients with primary Sjögren's syndrome. Focus scores as well as dry mouth may reflect lymphoproliferative activity in the lungs in patients with primary Sjögren's syndrome.

Analysis of the cell populations composing the mononuclear cell infiltrates in the labial minor salivary glands from patients with rheumatoid arthritis and sicca syndrome

ObjectivesSicca symptoms occur in around 30% of rheumatoid arthritis (RA) patients. Herein, we examined the characteristics of RA patients bearing sicca symptomatology (RA-sicca) with a special focus on the immunohistopathological features of their labial minor salivary gland (LMSG) biopsies. MethodsOur cohort included 100 consecutive RA patients which were interrogated using a sicca symptoms questionnaire. Positive responders were evaluated for ocular and oral dryness and underwent an LMSG biopsy. All samples were immunohistochemically evaluated for the presence and distribution of specific leukocyte subsets using appropriate markers and for the expression of certain immunoregulatory molecules by salivary gland epithelial cells. Positively stained and total mononuclear cells (MNC) were counted in the entire section. Counts were expressed as cell frequency (percentage of cell type number/total infiltrating MNC number). ResultsIn the majority (86.1%) of the 44 RA-sicca cases, periductal infiltrates were observed in LMSG biopsies. The frequencies of infiltrating cell subtypes and their correlation with lesion severity were different from that previously described in primary Sjögren’s syndrome (pSS). Moreover, DCs and ΜΦs frequencies were increased in RA-sicca patients who had a biopsy focus score <1 and absence of anti-Ro/anti-La autoantibodies, in contrast to what was observed for B cells. In about half of the biopsies, salivary gland epithelial cells expressed CD80/B7.1 molecules, most commonly in patients with a positive biopsy or anti-Ro/anti-La autoantibodies. ConclusionLMSG infiltrates composition in RA-sicca patients is distinct from that described in pSS. These differences, further attest to diverse pathophysiologic processes operating in these two entities.

Adipose tissue is prominent in salivary glands of Sjögren’s syndrome patients and appears to influence the microenvironment in these organs

A minor salivary gland (SG) biopsy with focal lymphocytic sialadenitis and a focus score of ≥1 is today’s widely accepted pathological finding confirming the SG component of Sjögren’s syndrome (SS). Adipocytes can occupy a large percentage of the SG area although little is known about their significance in SS lesions. This study aimed to characterise adipose tissue infiltration in labial SG biopsies from 27 SS patients and 28 non-SS sicca controls. Biopsies were evaluated by one oral pathologist and assessed for focus score, acinar atrophy, fatty replacement and non-specific chronic inflammation. Moreover, to explore the SG microenvironment, immunohistochemical staining of paraffin-embedded SG tissue was performed using interleukin-6 (IL-6). The fatty replacement was evident in all SS patients possessing autoantibodies (Ro/SSA and/or La/SSB) as well as a positive SG biopsy (focus score ≥1). Additionally, 62% of SS patients having autoantibodies but a negative biopsy showed fatty infiltration (FI) while non-SS controls demonstrated fatty replacement in only 32% of the cases. Overall, the SS group (mean age 53.0 years) had a significantly higher incidence (p value 0.005) of FI than the non-SS controls (mean age 54.8 years). Interestingly, adipocytes were located in IL-6 rich areas, and IL-6 positive adipocytes were detected. As fat deposition seems to be more recurrent in SGs affected by SS, we propose the assessment of adipose tissue replacement as a helpful tool for diagnostic evaluation in SS. Detection of IL-6 positive adipocytes suggests their involvement in immune reactions. Still, functional studies are needed to investigate the SG microenvironment further.

Brief Report: Patients With Primary Sjögren's Syndrome Who Are Positive for Autoantibodies to Tripartite Motif-Containing Protein 38 Show Greater Disease Severity.

Autoantibodies reactive with Ro52 (tripartite motif-containing protein 21 [TRIM21]) are detected in 70% of patients with primary Sjögren's syndrome (SS). TRIM21 belongs to a 34-member C-IV family of TRIM proteins. Although autoantibodies against other TRIM proteins within the C-IV family have been detected in the sera of patients with primary SS, their clinical relevance remains unclear. This study was undertaken to investigate the frequency of anti-TRIM38 in patients with primary SS and evaluate its association with various clinical measures of the disease. Serum samples from patients with primary SS (n = 235) and controls (n = 50) were analyzed for reactivity with in vitro-transcribed and -translated (35) S-methionine-labeled TRIM38 protein. The associations of anti-TRIM38 with various laboratory and clinical measures of primary SS were evaluated. Reactivity of anti-TRIM38 with different structural domains of TRIM38 was analyzed. Affinity-purified anti-TRIM38 antibodies were used to immunoprecipitate TRIM21. TRIM38-reactive autoantibodies were detected in the sera of 24 of the 235 patients with primary SS and 2 of the 50 controls. Anti-TRIM38 positivity was significantly associated with the presence of anti-Ro60, anti-Ro52, anti-La, rheumatoid factor, and hypergammaglobulinemia. Clinically, anti-TRIM38 was associated with significantly higher ocular surface staining scores, lower Schirmer's test scores, and minor labial salivary gland biopsy focus scores of ≥3.0. Anti-TRIM38 antibodies mainly recognized the cortactin-binding protein 2 (CortBP-2; amino acids 128-238) and the B30.2/SPRY (amino acids 268-465) domains on TRIM38. Affinity-purified antibodies to TRIM38-CortBP-2 and TRIM38-B30.2/SPRY domains reacted with TRIM21. Our data demonstrate that anti-TRIM38 specificity arising in a subset of patients with primary SS is associated with increased severity of the disease.

Local and Systemic IKKε and NF-κB Signaling Associated with Sjögren's Syndrome Immunopathogenesis.

The activated NF-κB signaling pathway plays an important role in pathogenesis of primary Sjögren's syndrome (pSS). The inhibitor of κB (IκB) kinase (IKK) family such as IKKα, IKKβ, IKKγ, and IKKε, is required for this signaling. Our aim was to investigate the role of IKKα/β/γ/ε in patients with untreated pSS. In minor salivary glands from pSS patients, phosphorylated IKKε (pIKKε), pIκBα, and pNF-κB p65 (p-p65) were highly expressed in ductal epithelium and infiltrating mononuclear cells by immunohistochemistry, compared to healthy individuals. pIKKα/β and pIKKγ were both negative. And pIKKε positively related to expression of p-p65. Furthermore, pIKKε and p-p65 expression significantly correlated with biopsy focus score and overall disease activity. Meanwhile, in peripheral blood mononuclear cells from pSS patients, pIKKε, total IKKε, pIKKα/β, and p-p65 were significantly increased by western blot, compared to healthy controls. However, there was no difference in IKKγ and IκBα between pSS patients and healthy individuals. These results demonstrated an abnormality of IKKε, IκBα, and NF-κB in pSS, suggesting a potential target of treatment for pSS based on the downregulation of IKKε expression and deregulation of NF-κB pathway.

FRI0296 Diagnostic performance of salivary gland ultrasonography in the early stages of pss in a real-life clinical setting

BackgroundRecently, convincing data have been published on the diagnostic value of salivary gland ultrasonography (SGUS) in primary Sjögren’s syndrome (pSS). A limited number of information are available on the performance...

Semi-quantitative evaluation of salivary gland function in Sjögren's syndrome using salivary gland scintigraphy

This retrospective study is designed to evaluate the diagnostic value of semi-quantitative parameters of salivary gland scintigraphy (SGS) in Sjögren's syndrome (SS) and explore the relationship between SGS parameters and salivary gland histopathologic manifestations. SGS and labial salivary gland biopsy were performed on 95 SS patients and 36 healthy age-matched and sex-matched volunteers. Uptake ratios at 15 min (UR(15)) and stimulated excretion fraction (EF) of each parotid and submandibular gland were calculated automatically from SGS; histopathologic grades were classified based on focal lymphocytic infiltration, and biopsy focus scores were calculated simultaneously. As a result, the UR(15) and EF of each salivary gland in SS patients were significantly lower than that in controls. Multivariate logistic regression equation was: logit p = 6.965 - 1.680 × UR(15) of left submandibular gland - 0.040 × EF of left parotid gland - 0.050 × EF of right submandibular gland. The receiver operating characteristic (ROC) curve validated high efficiency of this model with the area under curve of 0.911. And logistic regression analysis on combined original and validation cohorts confirmed its diagnostic value. Moreover, the EF of right parotid gland and both submandibular glands was correlated with histopathologic changes. Consequently, the semi-quantitative parameters of SGS may be helpful for diagnosing SS; UR(15) of left submandibular gland, EF of left parotid gland, and EF of right submandibular gland are more powerful predictor of SS. Besides, SGS parameters reflect the degree of salivary gland involvement, severe patients with low parameters would have high histopathologic grades and biopsy focus scores.

Systemic and Local Interleukin-17 and Linked Cytokines Associated with Sjögren’s Syndrome Immunopathogenesis

Recently recognized as a distinct CD4(+) T helper (Th) lineage, Th17 cells have been implicated in host responses to infections and in pathogenesis associated with autoimmune diseases. This cytokine is implicated in primary Sjögren's syndrome (pSS) immunopathology because of the increased levels of circulating interleukin (IL)-17 in pSS. Plasma and minor salivary glands (MSGs) from patients with pSS were therefore evaluated for CD4(+) T cells, T regulatory cells, IL-17, and supporting cytokines by immunohistochemistry, RT-PCR, and microbead assays. MSGs from pSS patients contain IL-17-expressing cells as a dominant population within inflammatory lesions. IL-17 protein expression progressively increased with higher biopsy focus scores (P < 0.0001), in parallel with detection by RT-PCR. Transforming growth factor-beta, IL-6 and IL-23, which are requisite promoters of Th17 differentiation, were found in abundance compared with the amounts in control tissues. Although transforming growth factor-beta is also a pivotal differentiation factor for immunosuppressive Foxp3(+) T regulatory cells (Tregs), an increase in Foxp3(+) Tregs was evident in biopsy specimens with mild and moderate inflammation but this increase was disproportionate to escalating pro-inflammatory Th17 populations in advanced disease. Furthermore, the Th17-centric cytokines IL-17, IL-6, IL-23, and IL-12 were significantly elevated in pSS plasma. These data identify a profusion of IL-17-generating cells and supporting cytokines within diseased pSS MSGs without a compensatory increase in immunomodulatory Tregs; this imbalance seems to foster a pathogenic milieu that may be causative and predictive of infiltrative injury and amenable to therapeutic intervention.

Foxp3 + T-Regulatory Cells in Sjögren's Syndrome : Correlation with the Grade of the Autoimmune Lesion and Certain Adverse Prognostic Factors

Sjögren's syndrome (SS) is a chronic autoimmune exocrinopathy associated with variable lymphocytic infiltration of the affected organs (primarily salivary and lacrimal glands) and broad clinical manifestations, including lymphoma development. To investigate the potential implication of Foxp3(+) T-regulatory cells in the regulation of SS inflammatory responses, we studied their incidence in the minor salivary glands (MSGs) and their relationship with histopathological and clinical disease parameters. Similar percentages of infiltrating Foxp3(+) cells were observed in the MSG lesions of all SS patients (n = 30) and non-SS sialadenitis controls (n = 7). Foxp3(+) cells were not detected in sicca-complaining controls with negative biopsy (n = 6). In SS patients, Foxp3(+) cell frequency varied according to lesion severity, with the highest and lowest frequencies obtained in intermediate and mild MSG lesions, respectively. In the peripheral blood of these patients, reverse distribution of Foxp3(+) cells was observed. Furthermore, the frequency of Foxp3(+) cells in the MSG lesions and peripheral blood was negatively associated (r = -0.6679, P = 0.0065). MSG-infiltrating Foxp3(+) cells were found to positively correlate with biopsy focus score (P = 0.05), infiltrating mononuclear cells, dendritic cells, and macrophages (P </= 0.024 each), and serum C4 levels (P = 0.0328), whereas lower Foxp3(+) cell incidence correlated with adverse predictors for lymphoma development, such as the presence of C4 hypocomplementemia (P = 0.012) and SG enlargement (tendency, P = 0.067). Our findings suggest that the Foxp3(+) T-regulatory cell frequency in the MSG lesions of SS patients correlates with inflammation grade and certain risk factors for lymphoma development.

Rates of infiltration by macrophages and dendritic cells and expression of interleukin‐18 and interleukin‐12 in the chronic inflammatory lesions of Sjögren's syndrome: Correlation with certain features of immune hyperactivity and factors associated with high risk of lymphoma development

To evaluate the expression profile of infiltrating macrophages and dendritic cells (DCs) as well as of interleukin-18 (IL-18) and IL-12 in the minor salivary gland (MSG) lesions of patients with Sjögren's syndrome (SS), and to assess the relationship of these factors with disease parameters. Macrophages, DCs, T cells, B cells, proIL-18, mature IL-18, and IL-12 were detected by single- and double-labeling immunohistochemistry in MSG specimens from 21 patients with primary SS (13 of 21 tested for IL-12), 7 patients with secondary SS, and 9 disease control patients. Expression profiles were assessed for correlations with various disease parameters, including adverse predictors of lymphoma development. MSGs from patients with SS (but not from disease controls) manifested increased infiltration by macrophages and DCs, strong expression of IL-18 by macrophages (particularly in B cell-rich areas and in germinal center-like structures in primary SS), and expression of IL-12 by mononuclear cell infiltrates. In primary SS, high infiltration by macrophages correlated with SG enlargement (P = 0.01). The DC infiltration rate correlated positively with the macrophage infiltration rate (P = 0.04), occurrence of SG enlargement (P = 0.03), and presence of C4 hypocomplementemia (P = 0.05), and inversely with serum C4 complement levels (P = 0.001). The rate of infiltration by IL-18-expressing cells correlated positively with biopsy focus scores (P < 0.001), larger infiltrates of macrophages (P = 0.01), DCs (P = 0.01), and B cells (P = 0.02), and SG enlargement (P = 0.02), and negatively with serum C4 complement levels (P = 0.02). The rate of infiltration by IL-12-expressing cells correlated inversely with that by IL-18-expressing cells (P = 0.001), biopsy focus scores (P = 0.003), and SG enlargement (P = 0.01), and positively with serum C4 complement levels (P = 0.05). In patients with primary SS, infiltration of the SG by macrophages and DCs and expression of IL-18 and IL-12 appear to play active roles in the expansion and organization of infiltrative injuries and have a correlation with certain predictors of lymphoma development.

Activation of the type I interferon system in primary Sjögren's syndrome: A possible etiopathogenic mechanism

The etiopathogenesis of primary Sjögren's syndrome (SS) is largely unknown. In other autoimmune diseases, type I interferon (IFN) may play a pivotal role by triggering and sustaining the disease process. We therefore aimed to determine whether patients with primary SS had an activated type I IFN system. Salivary gland biopsy specimens and sera from patients with primary SS were investigated for the occurrence of IFNalpha-producing cells and measurable IFNalpha levels, respectively. The ability of primary SS sera together with apoptotic or necrotic cells to induce IFNalpha production in normal peripheral blood mononuclear cells was examined. The IFNalpha inducer was characterized, and IFNalpha-producing cells were identified. Clinical data were correlated with the IFNalpha-inducing capacity of primary SS sera. Numerous IFNalpha-producing cells were detected in salivary gland biopsy specimens, despite low serum IFNalpha levels. Autoantibodies to RNA-binding proteins, combined with material released by necrotic or late apoptotic cells, were potent inducers of IFNalpha production in plasmacytoid dendritic cells (PDCs). This appeared to be attributable to RNA-containing immune complexes triggering PDCs by means of RNA and interaction with Fcgamma receptor IIa. The IFNalpha-inducing capacity of sera was associated with positive results of a labial salivary gland biopsy (focus score >/=1) and with dermatologic, hematologic, and pulmonary manifestations. Patients with primary SS have an activated type I IFN system. Although virus may initiate the production of IFN, the continued IFNalpha synthesis is caused by RNA-containing immune complexes that activate PDCs to prolong IFNalpha production at the tissue level. This IFNalpha promotes the autoimmune process by a vicious circle-like mechanism, with increased autoantibody production and formation of more endogenous IFNalpha inducers.

The diagnosis value of β2-microglobulin and immunoglobulins in primary Sjögren's syndrome

Salivary and serum concentrations of beta 2-microglobulin, salivary levels of the immunoglobulins, and salivary flow (as measured by a gravimetric method) were assessed in 34 patients and 11 controls. Of the 34 study patients, 16 had a primary form of Sjögren's syndrome (pSS) and 18 had sicca syndrome. The salivary and serum concentrations of beta 2-microglobulin and salivary levels of IgA and IgG were much higher in the patients with pSS than in controls or those with sicca syndrome (p < 0.001). Similarly, the salivary IgM levels of patients with pSS were higher (although at a lower degree of statistical significance) as compared to those of patients with sicca syndrome (p < 0.01) or controls (p < 0.05). No correlation was observed among the salivary flow and the salivary IgG and IgM levels, while there was a negative relationship (p < 0.01 with salivary IgA levels in all 45 patients considered as a whole. In 12 patients with pSS, the coefficient of correlation between the salivary gland biopsy focus score and the salivary (but not serum) concentration of beta 2-microglobulin was highly significant (p < 0.001). A similar relationship was observed with the IgG (p < 0.001) and IgM (p < 0.05) levels, but not IgA. In the diagnosis of pSS, the salivary IgA level demonstrates high sensitivity and low specificity. In contrast, serum and salivary concentrations of beta 2-microglobulin, salivary IgG, and to a lesser degree, salivary IgM have high specificity and positive predictive value.(ABSTRACT TRUNCATED AT 250 WORDS)