Minor Salivary Gland Biopsy Research Articles

SAT0191 Aberrant cytokine expression and severity of the infiltrates are reverted by rituximab therapy in salivary glands of patients with sjogren’s syndrome

BackgroundB lymphocytes are key players in the development of chronic autoimmune sialoadenitis and ectopic lymphoneogenesis is a milestone in the natural history of Sjögren’s syndrome (SS) (1). Much effort has...

THU0310 Comparison of Aecg 2002 and ACR 2012 Classification Criteria for SjöGren’s Syndrome in the Brittany Cohort

BackgroundNew classification criteria for primary Sjögren’s syndrome (pSS), based on the data from the SICCA registry, have been proposed in 2012 and approved by the American College of Rheumatology (ACR)....

AB0654 Diagnostic value of blood B-cell subset profiling for primary sjÖgren’s syndrome

BackgroundPrimary Sjögren’s syndrome (pSS) is a systemic auto-immune disease, characterised by abnormalities of B cell homeostasis. Several studies demonstrated that the repartition of blood B cell subsets is altered during...

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...

FRI0307 Vitamin d (VD) levels are associated with inflammation in minor salivary glands (MSG) and westergren sedimentation rate (W-ESR) in patients with sjögren’s syndrome

BackgroundSjögren’s syndrome (SS) is a chronic autoimmune exocrinopathy, manifested by a wide spectrum of clinical sequelae ranging from sicca to severe extra-glandular features. A hallmark of the pathogenesis of SS...

Importance of salivary gland focus score in the diagnosis of Sjögren's syndrome

To explore the correlation between labial salivary gland focus score (FS) and severity of Sjögren's syndrome patients. From January 2009 to December 2010, a total of 77 patients with primary Sjögren's syndrome were recruited to undergo minor salivary gland biopsy, Schirmer's test, unstimulated whole salivary flow, organ function and serological test. Focus score was calculated for all biopsy samples. And the correlation between focus score and serological test and organ function damage was evaluated. Their pathological examinations revealed focal lymphocytic sialadenitis (n = 62), 10 cases with non-specific or sclerosing chronic sialadenitis (n = 10) and normal features (n = 5). Among 62 cases with focal lymphocytic sialadenitis, 46 cases had FS ≥ 1 and another 16 FS < 1. The median FS was 2.4 ± 2.5 . FS ≥ 1 was strongly associated with unstimulated whole salivary flow rates and ocular staining score (P < 0.05), but not significantly with dry mouth or eyes. FS was significantly correlated with serum immunoglobin G (IgG), immunoglobin M (IgM) and rheumatoid factor level (P < 0.05). Those with positive anti-SSA had higher FS level than those with negative anti-SSA antibody (P < 0.05). In addition, FS level was not significantly associated with organ function damage. Prior to determining FS, distinguishing focal lymphocytic sialadenitis from other types of sialadenitis is essential in assessing salivary gland biopsy. And the FS level might be associated with disease activity and positive anti-SSA. No correlation exists between FS and organ function damage.

Parotidite recorrente juvenil… nem sempre é o que parece

Introduction: Juvenile recurrent parotiditis (JRP) is a relapsing inflammation of the parotid gland, usually associated with non-obstructive sialectasis. The Sjogren syndrome (SS), rare in children, may present at this age, in the form of recurrent parotiditis. Case Study: Female, 13 years, in the fourth episode of parotid swelling and pain, begins investigating: ultrasound of the parotid glands revealed heterogeneous texture and multiple punctiforme calcifications, high ANA (1:1280) title, with speckled pattern, auto-antibodies anti-SSA, anti-SSB and Rheumatoid Factor positive, hyper-gamaglobulinemia and elevated Immunoglobulin G. We also observed elevation of Creatinofosfoquinase, Glutamic Oxaloacetic Transaminase and Glutamic Pyruvic Transaminase. A minor salivary gland biopsy was consistent with a diagnosis of SS. Treatment was started with systemic steroids combining hydroxychloroquine during exacerbations, with clinical improvement. Discussion/conclusion: The age of onset of parotid swelling helps in differentiation between JRP idiopathic and other clinical entities. The muscle involvement occurs in primary SS and has a varied clinical and pathological spectrum, subclinical myositis occurs in a percentage that varies between 5% and 37%.

Gross Cystic Disease Fluid Protein-15(GCDFP-15)/Prolactin-Inducible Protein (PIP) as Functional Salivary Biomarker for Primary Sjögren’s Syndrome

BackgroundGross cystic disease fluid protein-15(GCDFP-15)/prolactin-inducible protein (PIP) is a secretory acinar glycoprotein of 14 KDa which we have recently described as significantly lower in salivary samples of patients with primary Sjögren’s syndrome (pSS) in comparison to healthy volunteers by proteomic analysis.Aims of the study(1) to validate our previous data on the decrease of GCDFP-15/PIP protein in a larger number of subjects with pSS (2) to integrate the proteomic results with complementary immunoassays in order better clarify the pathophysiological relevance of GCDFP-15/PIP in pSS exocrinopathy (3) to assess both the glandular expression of the GCDFP-15/PIP and the levels of glandular GCDFP-15/PIP mRNA in the patients’ minor salivary gland (MSG) biopsies in order to verify whether the observed reduction of GCDFP-15/PIP in saliva may be related to a decrease in the protein production.Patients and methodsA total of 123 salivary samples from patients affected by pSS, no-SS sicca syndrome and sex- age-matched healthy volunteers were analyzed by different proteomic techniques (SELDI-TOF-MS, 2DE, MALDI-TOF-MS). The expression of GCDFP-15/PIP was then validated by western blot analysis. Real Time PCR and immunohistochemistry for GCDFP-15/PIP in the minor salivary glands (MSG) biopsies were then carried out.ResultsBy using complementary proteomic analysis we found that a putative peak of 16547 m/z was among the best independent biomarkers for pSS able to discriminate between patients and healthy controls with a sensitivity of 96 % and a specificity of 70%, with a global cross validated error of 29%. We identified the peak as the GCDFP-15/PIP protein and verified that the intensity of GCDFP-15/PIP was significantly lower in pSS patients when compared to both no-SS sicca subjects and healthy controls (p<0.0001). GCDFP-15/PIP expression also correlated with both the salivary flow rate (r=0.312, p=0.023) and MSG biopsies focus score (r=−0.377, p=0.04). Finally, immunohistochemistry confirmed that GCDFP-15/PIP staining was faint in mucus acini and Real Time PCR showed that GCDFP-15/PIP mRNA was significantly lower in pSS patients when compared to both no-SS sicca subjects and healthy controls (p=0.023) thus supporting the hypothesis that the observed reduction of GCDFP-15/PIP in pSS saliva may be related to a decrease in the protein production.ConclusionIn this study by different complementary-omic techniques we confirmed the potential role of GCDFP-15/PIP as a novel biomarker for pSS. This finding might also be functionally important as GCDFP-15/PIP has previously been shown to bind to Aquaporin 5 (AQP5), a salivary gland water channel, critical to saliva formation that is known to be downregulated in pSS. It is likely that exploring the GCDFP-15/PIP/AQP5 axis will help better understand the mechanism of salivary gland dysfunction in pSS.

Efficacy and safety of rituximab treatment in early primary Sjögren's syndrome: a prospective, multi-center, follow-up study

IntroductionPrimary Sjögren’s syndrome (pSS) is an autoimmune disorder affecting exocrine glands; however, a subgroup of pSS patients experience systemic extra-glandular involvement leading to a worsening of disease prognosis. Current therapeutic options are mainly empiric and often translated by other autoimmune diseases. In the last few years growing evidence suggests that B-cell depletion by rituximab (RTX) is effective also in pSS. Patients with early active disease appear to be those who could benefit the most from RTX. The aim of this study was to investigate the efficacy and safety of RTX in comparison to disease modifying anti-rheumatic drugs (DMARDs) in early active pSS patients.MethodsForty-one patients with early pSS and active disease (EULAR Sjogren’s syndrome disease activity index, ESSDAI ≥ 6) were enrolled in the study. Patients were treated with either RTX or DMARDs in two different Rheumatology centers and followed up for 120 weeks. Clinical assessment was performed by ESSDAI every 12 weeks up to week 120 and by self-reported global disease activity pain, sicca symptoms and fatigue on visual analogic scales, unstimulated saliva flow and Schirmer’s I test at week 12, 24, 48, 72, 96, and 120. Laboratory assessment was performed every 12 weeks to week 120. Two labial minor salivary gland (MSG) biopsies were obtained from all patients at the time of inclusion in the study and at week 120.ResultsOur study demonstrated that RTX treatment results in a faster and more pronounced decrease of ESSDAI and other clinical parameters compared to DMARDs treatment. No adverse events were reported in the two groups. We also observed that RTX is able to reduce glandular infiltrate, interfere with B/T compartmentalization and consequently with the formation of ectopic lymphoid structures and germinal center-like structures in pSS-MSGs.ConclusionsTo our knowledge, this is the first study performed in a large cohort of early active pSS patients for a period of 120 weeks. We showed that RTX is a safe and effective agent to be employed in pSS patients with systemic, extra-glandular involvement. Furthermore, our data on pSS-MSGs provide additional biological basis to employ RTX in this disease.

Lymphoma Associated with Sjögren’s Syndrome

To the Editor, A 50-year-old woman visited the outpatient rheumatology department presenting with heel spurs and radiating pain in the legs and the right hip. She had sicca symptoms and morning stiffness lasting for 15 min. Her physical examination was normal other than positive FABERE test of the right hip. Routine biochemical tests and complete blood count were normal. Serological tests were positive for anti-nuclear antibodies (+2) with a speckled pattern, and positive for both anti-SS-A/Ro and anti-SS-B/ La antibodies. The erythrocyte sedimentation rate and C-reactive protein level were normal. The rheumatoid factor was 17.4 IU/mL (reference range: 0-14 IU/mL). The sacroiliac magnetic resonance findings were compatible with trochanteric bursitis. The results of Schirmer’s test were <5 mm for both eyes and a minor salivary gland biopsy showed focal periductal lymphoid aggregate. With these findings, the present case apparently met the criteria for the diagnosis of Sjogren’s Syndrome (SS) [1]. The patient was treated with hydroxychloroquine and artificial tear drops. Eighteen months later, the patient was admitted with painless swelling of the parotid glands. There was generalized peripheral lymphadenopathy in the neck, axillary, and inguinal regions. Excisional biopsies were obtained from the right inguinal lymph node, which revealed a high-grade, B-cell nonHodgkin lymphoma (NHL). The tumor tissue was composed of atypical round cells with pleomorphic vesicular nuclei undergoing frequent mitosis and eosinophilic cytoplasm (Figure 1). Immunohistochemically, neoplastic cells were positive for CD20, and the Ki-67 proliferation index was around 70%. She received 3 cycles of rituximab plus cyclophosphamide, epirubicin, vincristine, and prednisolone. Because of cardiotoxicity, she received 5 cycles of rituximab, cyclophosphamide, and Oncovin. After 2 months, her symptoms were resolved and her CT scan revealed a remarkable decrease in the generalized swelling of the lymph nodes. Five months later, a PET scan showed no findings consistent with recurrence or

Importance of minor salivary glands biopsy to diagnosis of Sjögren's syndrome

Importance of minor salivary glands biopsy to diagnosis of Sjögren's syndrome

Poster 46: Neonatal Hemochromatosis: The Importance of Minor Salivary Gland Biopsy in Diagnosis. The Cohen Children's Medical Center Experience

Neonatal hemochromatosis (NH) is a rare and severe neonatal liver disease associated with extrahepatic siderosis. A prompt diagnosis of NH is critical, as disease progression is rapid and early treatment is crucial. Consistently involved extrahepatic sites of iron deposition are minor salivary glands. Thus, biopsy of minor salivary gland lobules (MSGL) can offer a simple, low risk, rapid method to help establish a diagnosis. NH is also referred to as gestational alloimmune liver disease. Substantial evidence suggests it is the result of fetal liver injury.

Frequency of Complications and Usefulness of the Minor Salivary Gland Biopsy

Findings of specific antibodies and histopathology data are essential for the diagnosis of Sjögren syndrome (SS). Although the minor salivary gland biopsy (MSGB) is technically simple, it needs to be performed in a medical institution to avoid complications. ObjectiveTo determine the frequency of complications and the usefulness of this technique. Materials and methodsPatients who underwent a minor salivary gland biopsy for a possible diagnosis of SS at Rivadavia Hospital between October 2007 and May 2010 where included. The patients were seen a week and a month after the procedure for follow-up. ResultsFrequency of acute complications (n=186): 15 patients; 8.1%, 95% CI: 4.7–13.2 (Bleeding 7.5%, syncope 3.2%, hematoma 2.7%. No accidents occurred). Medium term complications (n=164): 16 patients: 9.75%, 95% CI: 5.9–15.6 (pain 7.32%, inflammation 3.66%, sensitivity disorders 3.05%, granuloma 1.22%). No infections or suture dehiscence occurred. Microscopic results: 154 biopsy reports were received: glandular 90.9%, 95% CI: 85–95 (typical, sialadenitis, grade III and IV infiltration). ConclusionsMSGB has very low frequency of medium term and acute complications and it has high usefulness.

The frequency of sicca symptoms and Sjögren's syndrome in patients with systemic sclerosis

The objectives are to detect the frequency of sicca symptoms and Sjögren's syndrome (SS) in patients with systemic sclerosis (SSc) based on the diagnostic criteria of the American-European Consensus Group (AECG) and to evaluate demographic, clinical and serologic characteristics. One hundred and eighteen SSc patients referred to our hospital were included in this study. All SSc patients were questioned with respect to sicca symptoms. Levels of rheumatoid factor (RF), anti-nuclear antibodies (ANA), anti-Ro and anti-La antibodies were measured; non-stimulated saliva amounts were recorded and Schirmer test and break-up time were applied to all patients. Minor salivary gland biopsy samples were obtained from those patients giving ≥3 positive answers to sicca symptom questions, patients with positive xerostomia/xerophthalmia test results, and patients with at least one antibody being positive. Patients presenting with grade 3 and/or grade 4 sialoadenitis based on Chisholm criteria were considered pathological. Sicca symptoms were present in 84 of 118 patients with SSc (71.2%). Minor salivary gland biopsy samples were obtained from 74 patients. Grade 3 and/or grade 4 sialoadenitis was detected in 40 (33.9%) patients and they were diagnosed with SS. Compared to patients diagnosed with SSc alone, systemic sclerosis patients diagnosed with SS had lower pulmonary hypertension and less diffuse lung involvement. Statistically significant difference was detected in terms of sclerodactylia and telangiectasia between SSc-SS and SSc patient groups (P=0.045 and P=0.011, respectively). Serological assessments revealed that in the SSc-SS group, 13 patients were anti-Ro antibody positive, six were anti-La antibody positive and 37 were anti-topoisomerase 1 antibody positive. RF, ANA and anti-centromere antibody levels were higher in the SSc-SS group. In the present study, highly frequent sicca symptoms and Sjögren's syndrome based on AECG criteria were noted in patients with systemic sclerosis. The SSc-SS patient group had less severe clinical course and lung involvement.

Predictors for the development of non-Hodgkin lymphoma in primary Sjögren's syndrome

Sjögren's syndrome (SS) is a complex autoimmune disease with multi-organ involvement. Its most serious complication is the development of non-Hodgkin lymphoma (NHL). In cohorts of unselected patients with long observation, this lifetime risk is estimated to be 5 to 15%, or approximately 20 times increased risk compared to the general population. Being able to identify patients prone to malignancy would significantly aid in the process of customised treatment and strategy for follow-up. Among the established predictors for lymphoma development in SS, we recognize recurrent or permanent swelling of major salivary glands (SG), lymphadenopathy, cryoglobulinemia, splenomegaly, low complement levels of C4 and C3, lymphopenia, skin vasculitis or palpable purpura, M-component in serum or urine, peripheral neuropathy, glomerulonephritis and elevated beta2-microglobulin. More recent suggestions include some genetic factors, CD4 lymphocytopenia, and ectopic germinal center-like structures in minor SG biopsies. Despite these predictors, there remains a need for defining algorithms for NHL screening and patient follow-up in SS.

Polyneuropathy Associated with the Diffuse Infiltrative Lymphocytosis Syndrome

Diffuse infiltrative lymphocytosis syndrome (DILS) arises in HIV-positive patients secondary to infiltration of lymphocytes into the peripheral tissues and produces the disease's characteristic symptoms-parotid gland enlargement and a sicca syndrome. Many patients, however, first seek medical attention for treatment of the extraglandular manifestations of DILS, most commonly interstitial pneumonitis. In this case report, we describe an atypical presentation of DILS characterized by polyradiculoneuropathy in the absence of parotid gland enlargement or interstitial pneumonitis. Minor salivary gland biopsy of the patient's lip confirmed a chronic inflammatory state with lymphoid aggregates within the minor salivary glands. He was started on prednisone with immediate improvement in his symptoms. This report illustrates for clinicians the diverse extraglandular manifestations of DILS and underscores the importance of considering it in the differential diagnosis of HIV-positive patients with a preserved CD4 count who present with peripheral neuropathy.

The expression of APRIL in Sjögren’s syndrome: aberrant expression of APRIL in the salivary gland

A proliferation-inducing ligand (APRIL) and B-cell activating factor (BAFF) are B-cell-related mediators and may play a role in the pathogenesis in SS. In this descriptive study we assessed the expression of APRIL and BAFF in the minor salivary gland and serum from SS patients. Paraffin-embedded minor salivary gland sections from SS patients, non-SS controls and healthy volunteers were analysed by immunohistochemistry. Digital image quantification was performed to evaluate the expression of BAFF, APRIL and transmembrane activator and CAML interactor. Furthermore, serum was analysed for soluble BAFF and APRIL levels by ELISA. All the data were also analysed for subjects with decreased and normal stimulated salivary flow independent of the classification. APRIL expression was lower in minor salivary gland biopsies from SS patients compared with healthy volunteers and to a lesser extent non-SS controls, whereas BAFF expression was similar in all groups. Soluble APRIL levels in serum were increased in SS patients and in subjects with decreased salivary flow independent of the classification. APRIL salivary gland tissue levels are decreased, suggesting that targeting this cytokine locally in the salivary glands would not benefit SS patients. Moreover, the discrepancy between local and systemic levels is striking and future research should assess this in more detail.

Detection of HTLV-1 in the Labial Salivary Glands of Patients with Sjögren’s Syndrome: A Distinct Clinical Subgroup?

To examine whether patients with Sjögren's syndrome (SS) can be distinguished based on the expression of human T cell lymphotrophic virus type I (HTLV-1) and, if so, whether the subgroups differ in their clinical features and serological measures. Polymerase chain reaction (PCR) and nested PCR were used to amplify viral DNA from peripheral blood mononuclear cells (PBMC) in 53 patients with SS, using primers from the HTLV-1 pX, p19, pol, and tax regions. Minor salivary gland biopsy specimens from 33 patients with SS were examined for the presence of HTLV-1 p19 or tax proteins immunohistochemically. The sociodemographic, glandular, and extraglandular manifestations, and laboratory findings including autoantibodies, complement, and immunoglobulin levels, were analyzed. The HTLV-1 tax gene was detected in PBMC samples from 2 of 53 patients (3.8%), whereas the HTLV-1 pX, p19, and pol genes were not expressed. As well, 100% of PBMC samples from 4 family members of patients in whom the tax gene was detected also expressed the tax gene. Immunohistochemical staining for HTLV-1 p19 and tax was seen in 10 out of 33 (30.3%) patients with SS each. Overall, 14 (42.4%) patients expressed HTLV-1 p19 or tax proteins, and they had lower rheumatoid factor and C3 levels (p = 0.015 and p = 0.005, respectively) and higher lymphocyte counts (p = 0.016). The prevalence of glandular and extraglandular manifestations did not differ between the HTLV-1-positive and negative patients. Our findings suggest that HTLV-1 in the salivary glands is involved in the pathogenesis of a subpopulation of SS, and HTLV-1-associated SS might have different immunological patterns than idiopathic SS.

Sjögren Sendromu ve Behçet Hastalığı Olan Bir Olguda Gelişen Sekonder Amiloidoz

Sjogren's syndrome (SS) is an autoimmune disease characterized by lymphocytic and plasma cell infiltration of lacrimal and salivary glands. Behcet's disease (BD) is a systemic disease characterized by recurrent orogenital apthous ulcerations and eye lesions like iridocyclitis. In this report, we describe a case that has both SS and BD associated with systemic AA type amyloidosis. The patient was a 70-year-old female who has been diagnosed with BD for twenty-two years and SS for ten years. She complained of nausea, vomiting, leg swelling and nocturia for the last few months. Duodenal biopsy was consistent with systemic AA type amyloidosis. Minor salivary gland biopsy demonstrated both systemic amyloidosis and autoimmune sialoadenitis. Both BD and SS can predispose amyloidosis deposition.

Primary Sjögren syndrome: report of a 10 years old girl with local edema and positivity of anti SS-A and anti SS-B autoantibodies

Sjogren-Larsson syndrome (SLS) is an autoimmune disease, uncommon in childhood. We report a case of SLS in a 10-year-old girl with a history of tumor, calor and rubor in the back of her toes almost every month, which resolved in 4-5 days without therapy. She did not complain of dry mouth or dry eyes. The laboratory findings showed high inflammation markers, rheumatoid factor 128 IU, Waaler-Rose 256 IU, anti nuclear antibody (ANA) 1/640, SSA (anti Sjogren antigen A) and SSB (anti Sjogren antigen B) positive and hypergammaglobulinemia. The Schirmer's test resulted to be pathologic, the ultrasonography images and biopsy of minor salivary glands revealed focal periductal lymphocytic infiltrate and sialoduct ectasia class IV of juvenile Sjogren syndrome. The juvenile Sjogren syndrome is frequently under-diagnosed. Clinical manifestations in children might be different from the adult form, although laboratory findings may be similar to those found in adults.