Dermatomyositis (DM) is characterized by progressive proximal limb weakness and typical skin manifestations. The histological findings that show perifascicular atrophy and deposition of membrane attack complex are pathognomic features of DM. Dermatomyositis is categorized into classical DM and non-classical DM, which includes amyopathic DM and DM sine dermatitis. DM sine dermatitis is seldom described because of its rarity, making the diagnosis more challenging. We report a case of DM sine dermatitis, a rare phenotype of DM.
Atrophy ; Complement Membrane Attack Complex ; Dermatitis* ; Dermatomyositis* ; Diagnosis ; Extremities ; Myositis* ; Phenotype* ; Skin Manifestations

Dermatomyositis (DM) is characterized by progressive proximal limb weakness and typical skin manifestations. The histological findings that show perifascicular atrophy and deposition of membrane attack complex are pathognomic features of DM. Dermatomyositis is categorized into classical DM and non-classical DM, which includes amyopathic DM and DM sine dermatitis. DM sine dermatitis is seldom described because of its rarity, making the diagnosis more challenging. We report a case of DM sine dermatitis, a rare phenotype of DM.
Atrophy ; Complement Membrane Attack Complex ; Dermatitis ; Dermatomyositis ; Diagnosis ; Extremities ; Myositis ; Phenotype ; Skin Manifestations

OBJECTIVETo explore the expression levels of terminal complement complex (C5b-9) and CD62p on platelets and the soluble C5b-9 (sC5b-9) level in serum in patients with PNH or PNH-aplastic anemia (AA).

METHODSSerum levels of sC5b-9, complement C3 and C4 were detected by using ELISA in 25 patients with PNH/PNH-AA. The quantities of C5b-9 and CD62p on the membrane of platelets were detected by flow cytometry.

RESULTS①In PNH/PNH-AA group, the serum sC5b-9 level [390.27(265.73-676.87) μg/L] was lower than that in control group [540.39(344.20-1 576.78) μg/L] (P<0.01). ②The platelet PNH clone (CD59⁻CD61⁺/CD61⁺) size [50.58(23.29-81.60)%] was bigger in the PNH/PNH-AA group than that [23.57(15.58-29.02)%] in control group (P<0.01). The percentages of C5b-9 deposition (C5b-9⁺CD61⁺/CD61⁺) were higher on the PNH clone platelets (CD59⁻CD61⁺) in the PNH/PNH-AA group [(17.53 ± 6.27)%] than those on the normal platelets (CD59⁺CD61⁺) in PNH patients 11.33±5.03）%］ and control [(10.88±3.58)%] group (P<0.01). ③ The expression of CD62p (CD62p⁺CD61⁺/CD61⁺) on PNH clone platelets in PNH patients [(61.98 ± 11.71)%] was higher than that on the normal platelets in PNH patients [(43.76±11.30)%] and control group [(38.23±18.07)%] (P<0.01). In addition, the expression of CD62p on normal platelets was higher in PNH patients than control (P<0.05). ④The deposition of C5b-9 positively correlated with the expression of CD62p on the platelets (r=0.559, P=0.002).

CONCLUSIONDeficiency of CD59 antigen on platelets in PNH patients may lead to the deposition of C5b-9 on its membrane and its dysfunction, which may contribute to thrombosis events in PNH.

Anemia, Aplastic ; Blood Platelets ; Clone Cells ; Complement Membrane Attack Complex ; Flow Cytometry ; Hemoglobinuria, Paroxysmal ; Humans ; P-Selectin ; Thrombosis

OBJECTIVE: To investigate the diagnostic significance of basophil activation test (BAT) in anaphylaxis to non-ionic contrast media through testing the content of CD63, mast cell-carboxypeptidase A3 (MC-CPA3), and terminal complement complex SC5b-9 of the individuals by testing their levels in the normal immune group and the anaphylaxis groups to β-lactam drugs and non -ionic contrast media. METHODS: The CD63 expression of basophilic granulocyte in blood was detected by flow cytometry. The levels of MC-CPA3 in blood serum and SC5b-9 in blood plasma were detected by ELISA. RESULTS: The CD63 expression of basophilic granulocyte in blood, the levels of MC-CPA3 and SC5b-9 of anaphylaxis to non-ionic contrast media and β-lactam drugs were significantly higher than that in normal immune group (P < 0.05). CONCLUSION There is activation of basophilic granulocytes, mast cells and complement system in anaphylaxis to non-ionic contrast media. BAT can be used to diagnose the anaphylaxis to non-ionic contrast media.
Anaphylaxis/diagnosis* ; Basophils/cytology* ; Carboxypeptidases A/metabolism* ; Complement Membrane Attack Complex/metabolism* ; Contrast Media ; Flow Cytometry ; Granulocytes/cytology* ; Humans ; Mast Cells/cytology* ; Tetraspanin 30/metabolism*

OBJECTIVETo investigate the expression of C5b-9 in the skeletal muscle blood vessels in patients with necrotizing myopathy and explore its role in the pathogenesis of this disease.

METHODSThe expression of C5b-9 and MHC-I in the skeletal muscular fibers and blood vessels in 4 patients with necrotizing myopathy was detected using enzymohistochemistry and immunohistochemistry.

RESULTSFocal or dispersive necrotic muscle fibers with obvious phagocytosis were observed in all the 4 patients. No inflammatory cell infiltration was found in the perimysium or perivascular regions. HE staining showed a decreased number of local small blood vessels, and the some small blood vessels showed thickened vascular walls. Immunohistochemistry detected prominent C5b-9 expression in the necrotic muscle fibers and the blood vessels, and diffuse strong C5b-9 expression was found in the vascular walls, vascular endothelial cells and the smooth muscle layer. No MHC-I deposition was detected in the muscular fibers and blood vessels.

CONCLUSIONC5b-9 contributes to the pathogenesis of necrotizing myopathy mediated by pathologies in the blood vessels.

Aged ; Complement Membrane Attack Complex ; metabolism ; Female ; Humans ; Male ; Middle Aged ; Muscle, Skeletal ; blood supply ; Muscular Diseases ; blood ; pathology ; Necrosis

The understanding of main mechanisms that determine the ability of immune privilege related to Sertoli cells (SCs) will provide clues for promoting a local tolerogenic environment. In this study, we evaluated the property of humoral and cellular immune response modulation provided by porcine SCs. Porcine SCs were resistant to human antibody and complement-mediated formation of the membrane attack complex (38.41+/-2.77% vs. 55.02+/-5.44%, p=0.027) and cell lysis (42.95+/-1.75% vs. 87.99 +/-2.25%, p<0.001) compared to immortalized aortic endothelial cells, suggesting that porcine SCs are able to escape cellular lysis associated with complement activation by producing one or more immunoprotective factors that may be capable of inhibiting membrane attack complex formation. On the other hand, porcine SCs and their culture supernatant suppressed the up-regulation of CD40 expression (p<0.05) on DCs in the presence of LPS stimulation. These novel findings, as we know, suggest that immune modulatory effects of porcine SCs in the presence of other antigen can be obtained from the first step of antigen presentation. These might open optimistic perspectives for the use of porcine SCs in tolerance induction eliminating the need for chronic immunosuppressive drugs.
Animals ; Antibodies, Heterophile/immunology ; Antibody Formation/*immunology ; Antigens, CD40/immunology ; Aorta/cytology ; Cell Line, Transformed ; Cell Survival/immunology ; Complement Membrane Attack Complex/immunology ; Complement System Proteins/immunology ; Dendritic Cells/cytology/immunology ; Endothelial Cells/cytology/immunology ; Epitopes/immunology ; Humans ; Immune Tolerance/*immunology ; Immunity, Cellular/*immunology ; Male ; Mice ; Mice, Inbred C57BL ; Sertoli Cells/cytology/*immunology ; Swine ; *Tissue Engineering ; Transplantation, Heterologous

PURPOSE: Local activation of the complement system plays a role in target organ damage. The aim of our study was to investigate the influence of cyclosporine (CsA)- induced renal injury on the complement system in the kidney. MATERIALS AND METHODS: Mice fed a low salt (0.01%) diet were treated with vehicle (VH, olive oil, 1mL/kg/day) or CsA (30mg/kg/day) for one or four weeks. Induction of chronic CsA nephrotoxicity was evaluated with renal function and histomorphology. Activation of the complement system was assessed through analysis of the expression of C3, C4d, and membrane attack complex (MAC), and the regulatory proteins, CD46 and CD55. CsA treatment induced renal dysfunction and typical morphology (tubulointerstitial inflammation and fibrosis) at four weeks. RESULTS: CsA-induced renal injury was associated with increased the expression of C3, C4d, and MAC (C9 and upregulation of complement regulatory proteins (CD 46 and CD55). Immunohistochemistry revealed that the activated complement components were mainly confined to the injured tubulointerstitium. CONCLUSION: CsA-induced renal injury is associated with activation of the intrarenal complement system.
Animals ; Antigens, CD45/analysis ; Antigens, CD46/analysis ; Antigens, CD55/analysis ; Complement C3/analysis ; Complement C4b/analysis ; Complement Membrane Attack Complex/analysis ; Complement System Proteins/*analysis ; Cyclosporine/*toxicity ; Disease Models, Animal ; Immunity, Innate/drug effects ; Immunoblotting ; Immunohistochemistry ; Immunosuppressive Agents/toxicity ; Kidney/*drug effects/immunology/pathology ; Kidney Diseases/*chemically induced/immunology ; Mice ; Microscopy, Confocal ; Peptide Fragments/analysis

Asthma ; blood ; Child ; Child, Preschool ; Complement Membrane Attack Complex ; analysis ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Intercellular Adhesion Molecule-1 ; blood ; Male ; Vascular Cell Adhesion Molecule-1 ; blood

To determine whether Smac/DIABLO (second mitochondrial activator of caspases/direct inhibitor of apoptosis protein-binding protein of low isoelectric point [PI]) and XIAP (X-chromosome-linked inhibitor of apoptosis protein) serve to regulate neuronal apoptosis following seizures, we investigated seizure-induced changes in caspase-9, Smac/DIABLO and XIAP protein expression and the in vivo effect of caspase-9 inhibition. Animals received unilateral intra-amygdaloid injection of kainic acid (0.5 microg) to induce seizures for 1 h. The seizures were then terminated by diazepam (30 mg/kg). Animals were killed 0, 2, 4, 8, 24 or 72 h following diazepam administration. The apoptotic and surviving neurons in hippocampus were observed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and cresyl violet staining, the expression of Smac/DIABLO, XIAP and caspase-9 was detected with immunofluorescence and western blot. The results showed that the levels of XIAP and the 46-kDa proenzyme form of caspase-9 were unaffected by the seizures. The expression of Smac increased at 2 h and the 37-kD cleaved fragment of caspase-9 was detected at 4 h, TUNEL-positive neurons appeared at 8 h and reached maximal at 24 h following seizure cessation within the ipsilateral (the same side as the intra-amygdaloid injection of kainic acid) CA3 subfield of the hippocampus. Intracerebroventricular infusion of caspase-9 inhibitor z-LEHD-fluoromethyl ketone (z-LEHD-fmk) significantly decreased TUNEL-positive neurons and increased the number of surviving cells. Caspase-9 immunoreactivity increased and Smac/DIABLO, XIAP immunoreactivity became extensive within the ipsilateral CA3 neurons. TUNEL-positive neurons and the alterations of the expression of Smac/DIABLO and XIAP within the ipsilateral CA3 were not detected within the contralateral hippocampus. These results suggest that seizures lead the translocation of Smac/DIABLO into the cytosol, the activation of caspase-9 and the change of subcellular locoalization of XIAP. These changes may play a role in the brain damage induced by seizures. Caspase-9 is possibly a potential therapeutic target in the treatment of brain injury associated with seizures.
Amygdala ; physiology ; Animals ; Caspase 9 ; Caspases ; biosynthesis ; genetics ; Complement Membrane Attack Complex ; Complement System Proteins ; Glycoproteins ; biosynthesis ; genetics ; Hippocampus ; metabolism ; Kainic Acid ; Limbic System ; Male ; Microinjections ; Protein Biosynthesis ; Proteins ; genetics ; Rats ; Rats, Sprague-Dawley ; Seizures ; chemically induced ; metabolism ; X-Linked Inhibitor of Apoptosis Protein

To explore the role of immune regulating cytokines in pathogenesis of the idiopathic thrombocytopenic purpura (ITP) and its clinical significance, the levels of IL-18, TNF-alpha and Sc5b-9 in plasma of 32 ITP patients and 18 normal individuals were detected using ELISA methods. The results showed that IL-18, TNF-alpha and sC5b-9 levels in plasma of ITP patients were higher than that in normal individuals. The level of IL-18 was positively correlated with the levels of TNF-alpha and sC5b-9. In conclusion, The rising levels of the IL-18, TNF-alpha and sC5b-9 were correlated with disorder of Th1/Th2 subsets, and may contribute to the immune dysfunction in ITP patients. The dynamic observation of these cytokines may be useful in directing the clinical treatment for ITP patients.
Adolescent ; Adult ; Child ; Child, Preschool ; Complement Membrane Attack Complex ; analysis ; Female ; Humans ; Interleukin-18 ; blood ; Male ; Middle Aged ; Purpura, Thrombocytopenic, Idiopathic ; immunology ; Tumor Necrosis Factor-alpha ; analysis