[The new classification criteria for spondylarthritis: implications in clinical practice]. / Place des nouveaux critères de classification des spondyloarthrites en pratique Clinique.

" Spondyloarthritis" consists of a group of several diseases sharing clinical, radiological and genetic similarities. Ankylosing spondylitis is the main representative of this group and is characterized by a predominant axial involvement. The presence of radiographic sacroiliitis is essential for the diagnosis of ankylosing spondylitis according to the modified New York criteria. Because the occurence of radiographic sacroiliitis takes 8 to 11 years, the diagnosis of spondyloarthritis is often delayed. Magnetic resonance imaging can depict sacroiliac joint inflammation before the appearance of radiographic damage thereby defining the concept of " non-radiographic axial spondylo-arthritis". This entity was defined by the axial spondyloarthritis classification criteria published by the Assessment of SpondyloArthritis international Society (ASAS). Some factors, such as elevated levels of C-reactive protein at baseline, have been identified as predictors of radiographic sacroiliitis progression, leading to a definite diagnosis of ankylosing spondylitis. These two entities show similar clinical expression (clinical features and activity levels), suggesting continuity between the two diseases. Non-radiographic forms most often affect women and patients with recent symptoms, and are therefore considered as a pre-radiographic status. If the use of magnetic resonance imaging is necessary for the identification of non-radiographic axial spondyloarthritis according to the ASAS criteria, the presumptive diagnosis is mainly based on complaints of inflammatory back pain. The presence of other typical clinical features, such as HLA B27 positivity and/or radiographic sacroiliitis increases the diagnostic probability and indicates the need for referral to a specialist.

Non-malignant causes of hypercalcemia in cancer patients: a frequent and neglected occurrence.

PURPOSE: Hypercalcemia is a frequent finding in cancer patients and can be observed in any type of cancer. The physician in charge of cancer patients often ignores non-malignant causes of hypercalcemia. Our objective was to review the causes of hypercalcemia in a large series of cancer patients. METHODS: We have retrospectively studied in a Cancer Centre all consecutive hypercalcemic (Ca> 10.5 mg/dl) patients over an 8-year period. Of 699 evaluated patients, 642 were analyzed after exclusion of patients whose hypercalcemia resolved after rehydration or who had a normal Ca level after correction for protein concentrations. Clinical information was gathered on the type of cancer, its histology, whether the disease was active or in complete remission, and on the presence of bone metastases. Biochemical data included serum Ca, P(i), proteins in all patients, PTH in most patients, and PTHrP, 25OH-Vitamin D, 1,25(OH)(2)-Vitamin D, TSH, and T4 in selected cases. RESULTS: By order of decreasing frequency, the main causes of hypercalcemia were cancer (69.0 %), primary hyperparathyroidism (24.6 %), hyperthyroidism (2.2 %), milk alkali syndrome (0.9 %), and sarcoidosis (0.45 %). In cancer-related causes, bone metastases accounted for 53.0 % of the cases, humoral hypercalcemia of malignancy (HHM) for 35.3 % while there were 11.7 % of cases apparently due to both HHM and bone metastases. Hypercalcemia was not due to cancer in 97 % (84/87) of the patients who were in complete remission. Even in patients with active neoplastic disease, the number of patients whose hypercalcemia was not due to cancer remained clinically relevant (115/555 = 20.5 %). In the 158 patients with primary hyperparathyroidism, 92 patients were in complete remission and 66 patients had active neoplastic disease. CONCLUSIONS: In this large series of hypercalcemia in cancer patients, the cause was not due to cancer in almost one third of the cases. Most patients considered to be in complete remission had hypercalcemia due to a benign condition. In that perspective, serum PTH determination is essential in the approach of hypercalcemic cancer patients since primary hyperparathyroidism is by far the first non-malignant cause of hypercalcemia.

Increased serum levels of high-mobility group box 1 (HMGB1) in primary Sjögren's syndrome.

OBJECTIVE: To determine serum levels of high-mobility group box 1 (HMGB1) in patients with primary Sjögren's syndrome (pSS) as compared to healthy volunteers and patients with sicca symptoms, and to determine whether serum HMGB1 levels are correlated with disease activity in pSS. METHODS: Serum HMGB1 levels were determined by enzyme-linked immunosorbent assay (ELISA) in 101 patients with pSS, 13 patients with sicca symptoms, and 40 healthy volunteers. Clinical and laboratory variables were also analysed and serum HMGB1 levels were correlated with the Sjögren's Syndrome Disease Activity Index (SSDAI). RESULTS: The serum levels of HMGB1 were significantly increased in pSS patients as compared to patients with sicca symptoms and healthy controls (p = 0.04 and p = 0.01, respectively). In the subgroups of patients with anti-SSA autoantibodies, the serum levels of HMGB1 were significantly higher than those in the subgroup of pSS patients who were anti-SSA negative and in healthy controls and patients with sicca symptoms (p < 0.001, p < 0.001, and p = 0.004, respectively). There was no significant correlation between serum HMGB1 levels (in pSS patients with anti-SSA autoantibodies) and SSDAI score (r = 0.03, p = 0.83). Patients with active disease had higher HMGB1 levels than patients with low disease activity (p = 0.04), but HMGB1 levels did not correlate with the SSDAI. CONCLUSION: Serum HMGB1 levels are increased in pSS patients and more specifically in patients with SSA autoantibodies. There was, however, no correlation of HMGB1 with the SSDAI.

Relationship between aquaporin-5 expression and saliva flow in streptozotocin-induced diabetic mice?

OBJECTIVE: To investigate the expression and distribution of AQP5 in submandibular acinar cells from sham- and streptozotocin (STZ)-treated mice in relation to the salivary flow. METHODS: Mice were sham or STZ injected. Distribution of AQP5 subcellular expression in submandibular glands was determined by immunohistochemistry. AQP5 labelling indices (LI), reflecting AQP5 subcellular distribution, were determined in acinar cells. Western blotting was performed to determine the expression of AQP5 in submandibular glands. Blood glycaemia and osmolality and saliva flow rates were also determined. RESULTS: AQP5 immunoreactivity was primarily located at the apical and apical-basolateral membranes of submandibular gland acinar cells from sham- and STZ-treated mice. No significant differences in AQP5 protein levels were observed between sham- and STZ-treated mice. Compared to sham-treated mice, STZ-treated mice had significant increased glycaemia, while no significant differences in blood osmolality were observed. Saliva flow rate was significantly decreased in STZ-treated mice as compared to sham-treated mice. CONCLUSIONS: In STZ-treated mice, significant reduction in salivary flow rate was observed without any concomitant modification in AQP5 expression and localization.

Link between inflammation and aquaporin-5 distribution in submandibular gland in Sjögren's syndrome?

OBJECTIVE: To determine whether a link exists between inflammation and aquaporin-5 distribution in submandibular glands from three animal models for Sjögren's syndrome: IQI/JIC, r1ΔT/r2n and non-obese diabetic mice. METHODS: Mice of different ages were used. Inflammatory infiltrates were quantified using the focus score. Acinar aquaporin-5 subcellular distribution was determined by immunohistochemistry and quantified using labelling indices. RESULTS: Minor inflammatory infiltrates were present in r1f/r2n mice. Massive inflammatory infiltrates and acinar destruction were observed in 24-week-old non-obese diabetic mice, 10-and 13-month-old IQI/JIC mice and some r1ΔT/r2n mice. Aquaporin-5 immunoreactivity was primarily apical in submandibular glands from 8- and 24-week-old Balb/C mice, 8-week-old non-obese diabetic mice, 2-, 4- and 7-month-old IQI/JIC mice and r1f/r2n mice. In contrast, decreased apical aquaporin-5 labelling index with concomitant increased apical-basolateral, apical-cytoplasmic and/or apical-basolateral-cytoplasmic aquaporin-5 labelling indices was observed in 24-week-old non-obese diabetic, 10- and 13-month-old IQI/JIC and r1ΔT/r2n mice with a focus score≥1. CONCLUSIONS: Altered aquaporin-5 distribution in submandibular acinar cells from IQI/JIC, non-obese diabetic and r1ΔT/r2n mice with a focus score≥1 appears to be concomitant to the presence of inflammatory infiltrates and acinar destruction.

Usefulness of mouse models to study the pathogenesis of Sjögren's syndrome.

Sjögren's syndrome (SS) is an autoimmune disorder characterized by ocular and oral dryness as well as systemic manifestations. The immunopathogenesis of SS is complex with different intricate factors. Because of the delay in the appearance of symptoms and due to ethical issues it is very difficult to study the wide array of factors intervening in the pathogenesis of SS in human patients. To circumvent this problem, different animal models have been elaborated for studying the different subsets of the aspects of the physiopathology of this disease. In this review, we focus on the mouse models that have been established to deepen our insight into the immunopathogenesis of SS.