Progress of P-selectin glycoprotein ligand-1 in kidney diseases

P-selectin glycoprotein ligand-1 (PSGL-1) is an adhesion molecule mainly expressed on the surface of leukocytes and platelets, which plays a vital part in immune recognition, inflammatory response and thrombosis. The prevalence of chronic kidney disease (CKD) is increased gradually and it has been one of major diseases that threaten the world's public health. In addition, its etiology is complicated, and most of the pathogenesis is incompletely understood. Researches show that PSGL-1 participates in the development of kidney diseases in a variety of ways, and its mechanism may involve signaling pathways such as TGF-β1/Smad and PI3K/AKT/GSK-3β, as well as key renal regulators such as connective tissue growth factor and chemokine (C-C motif) ligand 2. This review summarizes the research progress of PSGL-1 in renal fibrosis, lupus nephritis, obesity-related kidney disease and acute kidney injury.     

The presence of antiphospholipid antibodies in healthy Bernese Mountain Dogs

Background

The role of antiphospholipid antibodies in the prolonged activated partial thromboplastin time (aPTT) previously identified in healthy Bernese Mountain Dogs remains unknown. In people, an isolated prolonged aPTT without evidence of bleeding might be because of a thrombophilic condition caused by antiphospholipid antibodies.

Objective

To examine if prolonged aPTT in healthy Bernese Mountain Dogs is because of antiphospholipid antibodies.

Animals

Twenty‐two healthy Bernese Mountain Dogs and 10 healthy adult dogs of various breeds.

Methods

Prospective case control study. Healthy Bernese Moutain Dogs were examined twice over 6 months. Dogs were investigated for the presence of lupus anticoagulants and anticardiolipin (aCL) antibodies by the use of multiple aPTT tests with low and high lupus anticoagulant sensitivities, a mixing study, and an ELISA test for aCL antibody optical density to detect solid phase antiphospholipid antibodies.

Results

In all, 15 of 22 healthy Bernese Mountain Dogs were positive for lupus anticoagulants. The Bernese Mountain Dogs had markedly higher levels of aCL antibodies compared with the control dogs (P = .006). In all, 7 of 21 of the Bernese Mountain Dogs were positive for both lupus anticoagulants and aCL antibodies, whereas 4 of 21 Bernese Mountain Dogs were negative for both.

Conclusions and Clinical Importance

Lupus anticoagulants and aCL antibodies could be the cause of prolonged aPTT in healthy Bernese Mountain Dogs. The importance of the antiphospholipid antibodies in the dogs remains unknown.     

Differential expression profiling of proteome for systemic lupus erythematosus with quantitative proteomic technique

AIM: To identify and quantify the total proteins in peripheral blood mononuclear cells (PBMC) of systemic lupus erythematosus (SLE) patients with quantitative proteomic technique, and to establish a differential expression profile of proteome for SLE. METHODS: Four-plex isobaric tags for relative and absolute quantification coupled with multiple chromatographic fractionation and tandem mass spectrometry were used to analyze the total proteins in PBMC from healthy controls and the patients of stable SLE, active SLE and rheumatoid arthritis. The proteins were identified by database searching with peptide mass fingerprinting. The differential expression of the proteins was compared. RESULTS: More than 400 proteins were identified. Compared with healthy controls, 44 proteins were discovered to be significantly expressed by more than 2 folds in stable SLE and active SLE, among which 9 proteins were up-regulated and 35 proteins were down-regulated. Compared with rheumatoid arthritis group, 52 proteins displayed 2 or more folds of changes in stable SLE and active SLE, including 19 up-regulated proteins and 33 down-regulated ones. The up-and down-regulated proteins between active SLE and stable SLE were 17 and 13, respectively. CONCLUSION: Quantitative proteomic technique is efficiently applicable for protein identification and relative quantitation in human peripheral blood mononuclear cells. Determination of the differentially expressed proteomic profile of SLE is helpful for better understanding the pathogenesis of SLE and developing new strategies for diagnosis and treatment of SLE.     

Association of Fas promoter-670 polymorphism with systemic lupus erythematosus in southern Chinese

AIM: To investigate whether Fas promoter-670 polymorphism is associated with systemic lupus erythematosus(SLE) in Southern Chinese. METHODS: 103 SLE patients and 110 controls were studied. Fas promoter -670 polymorphism was typed by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). RESULTS: No statistically significant differences were found when Fas promoter -670 genotype and allele frequencies were compared between the SLE and the controls. Similarly, no significant differences were seen between the male and female SLE and the controls, the SLE with lupus nephritis (LN) and the controls, the SLE with LN and the SLE without LN. CONCLUSION: Fas promoter -670 polymorphism does not appear to be associated with susceptibility to SLE in Southern Chinese.     

Systemic lupus erythematosus in a cat: fulfillment of the American Rheumatism Association criteria with supportive skin histopathology

Systemic lupus erythematosus (SLE) was diagnosed in a 9-year-old castrated male Persian cat. The cat described is the first to fulfil four of 11 American Rheumatism Association criteria for the diagnosis of SLE in humans (symmetrical facial dermatitis, thrombocytopenia, positive antinuclear antibodies, oral ulceration) with supportive skin histopathology. Haematological abnormalities included a mild anaemia and severe thrombocytopenia. Skin disease consisted of symmetrical multifocal alopecia with crusting, predominantly on the face. Histopathology of the skin revealed interface dermatitis and interface folliculitis with follicular atrophy. Complete remission was obtained with corticosteroid therapy.     

Presumed lupus erythematosus cells identified in bronchoalveolar lavage fluid from a Mexican Hairless dog

A neutered male Mexican Hairless dog was presented for generalized weight loss and weakness. Initial laboratory testing and diagnostic imaging revealed thrombocytopenia and an interstitial to miliary lung pattern affecting all lung fields. Mild joint effusion was found on physical examination affecting the stifle, tarsal, carpal, and elbow joints. Examination of synovial fluid demonstrated an inflammatory polyarthropathy in 3 joints. Cytocentrifuged and direct preparations of the bronchoalveolar lavage (BAL) fluid sample were made and cells consistent with lupus erythematosus (LE) cells and ragocytes were found. Based on these findings, the anti‐nuclear antibody (ANA) titer was determined as 1:640. A clinical diagnosis of systemic LE was made based on the satisfaction of 2 major criteria (thrombocytopenia and inflammatory polyarthritis), 4 minor criteria (central nervous system signs, lymphadenopathy, fever of unknown origin, and pleuritis), positive ANA titer, and the identification of presumed LE cells in BAL fluid. This case report highlights a novel finding of LE cells in respiratory secretions and provides a review of diagnostic criteria of systemic LE.     

Protective effect of curcumin on MRL/lpr mice with lupus nephritis and its mechanism

AIM To observe the effect of curcumin （Cur） on lupus nephritis （LN） and its possible mechanism. METHODS Thirty 10-week-old MRL/lpr lupus mice were randomly divided into MRL/lpr group, Cur-L and Cur-H group with 10 mice in each group, and C57BL/6 mice （n=10） served as normal control （NC） group. The mice in Cur-L group and Cur-H group were given intragastric administration of Cur at 100 and 200 mg·kg^-1·d^-1 for 12 weeks, respectively, and the same volume of normal saline was given to the mice in NC group and MRL/lpr group. The urine protein was detected, and the morphological changes of the renal tissue were observed by HE staining after treatment. The levels of serum creatinine （SCr）, blood urea nitrogen （BUN） and serum anti-double-stranded DNA （dsDNA）, and interleukin-1β （IL-1β）, IL-6 and tumor necrosis factor-α （TNF-α） levels in serum and renal tissues were detected. The protein levels of p-IκB, NF-κB, NLRP3 and caspase-1 in the renal tissues were determined by Western blot. RESULTS Compared with MRL/lpr group, the content of urine protein in Cur groups was significantly reduced, and the renal injury was relieved. The SCr, BUN, serum anti-dsDNA, and the serum and renal levels of IL-1, IL-6 and TNF-α were all significantly reduced, and the protein levels of p-IκB, NF-κB, NLRP and caspase-1 in the renal tissue were significantly decreased （P<0.05）. CONCLUSION Cur has a certain protective effect on the kidney of MRL/lpr mice, and its mechanism may be related to the inhibition of NF-κB and NLRP3 signaling pathways.