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PubMed1989

Secretion of the terminal complement proteins, C5-C9, by human platelets.

The terminal complement components, C8 and C9, and to a lesser extent C5, C6, and C7, but minimal amounts of C3, were shown to be associated with washed human platelets. In unactivated platelets, the complement components were detected in the platelet pellet by hemolytic assays after centrifugation and disruption of the platelets by freeze-thawing. However, after platelets had been activated by collagen, thrombin, or aggregated IgG to induce aggregation, the complement components were released into the supernatant. The rank order of hemolytic activity of C9, C8, C7, C6, and C5 detected in the supernatants of activated platelets was quite different from that found in serum from the same donors, in the same assays. In particular, the serum C7 hemolytic titer was more than twice the serum C9 hemolytic titer, whereas the activity of C9 detected from platelets was more than twice that of C7. This argues against a purely nonspecific uptake of these proteins by platelets from plasma. The functional role of terminal complement components released from platelets during activation is unknown, but it is tempting to speculate that these proteins may have a role in platelet-dependent immunological tissue injury. Because the C5b-9 membrane attack complex activates platelets, it is possible that release of terminal complement proteins serves to amplify platelet activation and may also play a role in diseases in which complement membrane attack complexes have been implicated.

Blood Platelets↗
PubMed2003

CD59a deficiency exacerbates accelerated nephrotoxic nephritis in mice.

CD59 is a complement regulatory protein that inhibits the terminal part of the complement system, the membrane attack complex (MAC), a mediator of renal injury. Mice deficient in the Cd59a gene (mCd59a-/-) were used to investigate the role of CD59 in experimentally induced accelerated nephrotoxic nephritis, a model of immune complex-mediated glomerulonephritis. After accelerated nephrotoxic nephritis was induced by administration of sheep nephrotoxic globulin, mCd59a-/- mice and strain-matched controls on two genetic backgrounds, 129/Sv x C57BL/6 and 129/Sv, were examined. For both, mCd59a-/- mice developed significantly greater glomerular cellularity than wild-type (WT) mice at day 5 after administration. At day 10 post-administration, mCd59a-/- mice exhibited more glomerular thrombosis than WT mice (thrombosis score, 1.8 [range, 1.4 to 4.0] versus 0.8 [range, 0.2 to 1.5] quadrants thrombosed per glomerulus, respectively; P = 0.0006). In the majority of experiments, mCd59a-/- mice also had significantly more proteinuria than controls; however, there was no difference in serum creatinine or albumin. Quantitative immunofluorescence of kidney sections revealed significantly more C9 (as a marker of MAC) deposition within glomeruli of mCd59a-/- mice than WT controls (P < 0.001). There was no difference in deposition of C3 and sheep IgG between the two experimental groups. The lack of CD59a, by allowing unregulated MAC deposition, exacerbates the renal injury in this model of immune complex-mediated glomerulonephritis.

Animals↗
PubMed1996

Identification of disulfide bonds in the ninth component (C9) of human complement.

C9 is the most abundant protein of the membrane attack complex of complement. By means of limited proteolysis, different chromatographic techniques, a thiol-specific fluorescence assay, amino acid analysis, and Edman degradation 9 out of 12 disulfide bridges are definitely assigned (Cys22-Cys57, Cys33-Cys36, Cys67-Cys73, Cys121-Cys160, Cys233- Cys234, Cys359-Cys384, Cys489-Cys505, Cys492-Cys507, Cys509-Cys518). Weaker evidence permits to reduce the number of possible configurations for the remaining 3 cystines (Cys80-Cys91, Cys86-Cys104, Cys98-Cys113, or Cys80-Cys91, Cys86-Cys113, Cys98-Cys104). These findings are discussed in comparison with the strongly related components C6, C7, C8alpha, and C8beta.

Amino Acid Sequence↗
PubMed1993

Membrane defence against complement lysis: the structure and biological properties of CD59.

The complement system is an important branch of the innate immune response, constituting a first line of defence against invading microorganisms which activate complement via both antibody-dependent and -independent mechanisms. Activation of complement leads to (a) a direct attack upon the activating cell surface by assembly of the pore-forming membrane attack complex (MAC), and (b) the generation of inflammatory mediators which target and recruit other branches of the immune system. However, uncontrolled complement activation can lead to widespread tissue damage in the host, since certain of the activation products, notably the fragment C3b and the C5b-7 complex, can bind nonspecifically to any nearby cell membranes. Therefore it is important that complement activation is tightly regulated. Our own cells express a number of membrane-bound control proteins which limit complement activation at the cell surface and prevent accidental complement-mediated damage. These include decay-accelerating factor, complement receptor 1 and membrane cofactor protein, all of which are active at the level of C3/C5 convertase formation. Until recently, cell surface control of MAC assembly had been attributed to a single 65-kD membrane protein called homologous restriction factor (alternatively named C8-binding protein and MAC-inhibiting protein). However a second MAC-inhibiting protein has since been discovered and it is now clear that this protein plays a major role in the control of membrane attack. This review charts the rapid progress made in elucidating the protein and gene structure, and the mechanism of action of this most recently discovered complement inhibitor, CD59.

Animals↗
PubMed2004

CD59a is the primary regulator of membrane attack complex assembly in the mouse.

Gene-deleted mice have provided a potent tool in efforts to understand the roles of complement and complement-regulating proteins in vivo. In particular, mice deficient in the membrane regulators complement receptor 1-related gene/protein y, decay-accelerating factor, or CD59 have demonstrated homeostatic relevance and backcrossing between the strains has revealed cooperativity in regulation. In mouse, genes encoding decay-accelerating factor and CD59 have been duplicated and show differential expression in tissues, complicating interpretation and extrapolation of findings to man. The first described form of CD59, CD59a, is broadly distributed and deletion of the cd59a gene causes a mild hemolytic phenotype with increased susceptibility in complement-mediated disease models. The distribution of the second form, CD59b, was originally described as testis specific, but later by some as widespread. Deletion of the cd59b gene caused a severe hemolytic and thrombotic phenotype. To apply data from these mouse models to man it is essential to know the relative distribution and functional roles of these two forms of CD59. We have generated new specific reagents and used them in sensitive quantitative analyses to comprehensively characterize expression of mRNA and protein and functional roles of CD59a and CD59b in wild-type (wt) and CD59a-negative mice. cd59b mRNA was detected only in testis and, at very low levels, in bone marrow. CD59b protein was present on mature spermatozoa and precursors and, in trace amounts, erythrocytes. Erythrocyte CD59b did not inhibit complement lysis except when CD59a was absent or blocked. These data confirm that CD59a is the primary regulator of complement membrane attack in mouse.

Animals↗
PubMed1996

Molecular mechanisms of glomerular injury in rat experimental membranous nephropathy (Heymann nephritis)

The molecular pathogenesis of human membranous nephropathy (MN) is unknown, despite the relatively high incidence and severity of this glomerular immune disease. Heymann nephritis (HN) in rats is considered an instructive experimental model of MN. This study summarizes current molecular aspects of two key events common to both MN and HN, i.e., formation of characteristic subepithelial immune deposits in the glomerular basement membrane (GBM), and development of glomerular capillary wall damage resulting in proteinuria. In HN, the antigenic targets of immune deposit-forming antibodies were identified in cell membranes of glomerular epithelial cells as a 515-kd glycoprotein (megalin, or gp330), which is a polyspecific receptor related to the low-density lipoprotein receptor family, and an associated 44-kd protein (receptor associated protein, RAP). One epitope was recently narrowed to 14 amino acids in RAP, and several others on megalin/gp330 are under investigation. Proteinuria requires formation of the complement C5b-9 membrane attack complex, which is presumably triggered by antibodies directed against lipid antigens that associate with immune deposit-forming megalin/gp330 immune complexes. Sublytic C5b-9 attack on glomerular epithelial cells causes upregulation of expression of the NADPH oxidoreductase enzyme complex by glomerular cells, which is translocated to their cell surfaces, similar to activated neutrophil granulocytes in the respiratory burst reaction. Subsequently, reactive oxygen species (ROS) are produced locally, which reach the GBM matrix. Here formation of lipid peroxidation (LPO) adducts is found, preferentially on monomeric and dimerized NCl domains of covalently crosslinked Type IV collagen. These structural changes within the GBM could be of functional relevance because treatment with the potent LPO-antagonist probucol reduces proteinuria by < 80%. Intact or fragmented apoprotein E-containing lipoproteins were identified as potential sources of the polyunsaturated lipids required for the production of LPO adducts. Lipoproteins accumulate within immune deposits and show signs of oxidative damage, similar to oxidized LDL within atherosclerotic lesions. Collectively, the results obtained so far in HN permit the compilation of a sequence of events, linking formation of immune deposits with proteinuria. However, despite this relatively detailed knowledge of pathogenic events in HN, the bridge to human NM remains to be built.

Animals↗
PubMed1993

Isolation of erythrocyte membrane inhibitor of reactive lysis type II. Identification as glycophorin A.

When incubated with activated CoF and normal human serum (as the C source), a portion of the E from most patients with PNH are hemolyzed. In contrast, normal E are completely resistant to this form of C-mediated cytolysis called reactive lysis. This observation implies that normal E express membrane proteins that inhibit reactive lysis. In previous studies, we have shown that when E proteins are subjected to anion exchange chromatography, two peaks of inhibitory activity are observed. We isolated the inhibitor from the first peak and identified it as an 18-kDa protein that we call MIRL (CD59). The purpose of the studies presented herein was to isolate the inhibitory factor (MIRL type II) from the second peak. After anion exchange and gel filtration chromatography, aliquots of the fractions containing MIRL II activity were subjected to preparative SDS-PAGE (nonreducing conditions), and protein was eluted from gel slices electrophoretically. Inhibitory activity was found primarily in two adjacent slices, corresponding to an M(r) range of 84-51 kDa. When MIRL II was analyzed by SDS-PAGE and silver staining, two prominent bands representing proteins with M(r) of 77 and 39 kDa were observed under both reducing and nonreducing conditions. This behavior in SDS-PAGE is characteristic of GP-A, which migrates primarily as a nondisulfide-linked homodimer in equilibrium with a monomeric form. Immunoblotting studies confirmed that MIRL II is GP-A. The protein caused a concentration-dependent inhibition of reactive lysis, with approximately 100 ng producing 50% inhibition. GP-A inhibited reactive lysis by blocking the formation or binding of C5b-7, and this inhibitory activity was immunoprecipitated by monoclonal anti-GP-A. Furthermore, GP-A that was isolated by affinity chromatography also inhibited reactive lysis. These studies demonstrate that the major E sialoglycoprotein functions as an inhibitor of the membrane attack complex of C.

Animals↗
PubMed2005

The ontogenic transcription of complement component C3 and Apolipoprotein A-I tRNA in Atlantic cod (Gadus morhua L.)--a role in development and homeostasis?

The complement system is important both in the innate and adaptive immune response, with C3 as the central protein of all three activation pathways. Apolipoprotein A-I (ApoLP A-I), a high-density lipoprotein (HDL), has been shown to have a regulatory role in the complement system by inhibiting the formation of the membrane attack complex (MAC). Complement has been associated with apoptotic functions, which are important in the immune response and are involved in organ formation and homeostasis. mRNA probes for cod C3 and ApoLP A-I were synthesized and in situ hybridisation used to monitor the ontogenic development of cod from fertilised eggs until 57 days after hatching. Both C3 and ApoLP A-I transcription was detected in the central nervous system (CNS), eye, kidney, liver, muscle, intestines, skin and chondrocytes at different stages of development. Using TUNEL staining, apoptotic cells were identified within the same areas from 4 to 57 days posthatching. The present findings may suggest a role for C3 and ApoLP A-I during larval development and a possible role in the homeostasis of various organs in cod.

Animals↗
PubMed1995

Passive transfer of autoantibodies from a patient with mutilating epidermolysis bullosa acquisita induces specific alterations in the skin of neonatal mice.

BACKGROUND: Epidermolysis bullosa acquisita is a subepidermal bullous disease characterized by IgG autoantibodies directed against type VII collagen in anchoring fibrils. These autoantibodies are believed to play an important role in the pathogenesis of sub-lamina densa blister formation in this disease. OBSERVATIONS: We describe a patient with epidermolysis bullosa acquisita who has developed mutilating acral involvement with early syndactyly and extensive scarring lesions of the scalp. The patient's serum contains IgG autoantibodies that bind the dermal side of 1-mol/L sodium chloride-separated human skin (at a titer up to 5120), as determined by indirect immunofluorescence microscopy, and type VII collagen, as determined by immunoblot. The severity of this patient's disease and the height of his immune response to type VII collagen prompted us to assess the pathogenicity of his autoantibodies in a murine model. Purified IgG from our patient (or that from a healthy volunteer who served as a control) was administered subcutaneously to BALB/c mice (10 mg/g of body weight) on 2 consecutive days. Light microscopy of normal-appearing skin showed pronounced dermal edema and a dense granulocyte-rich infiltrate in the superficial dermis. Deposits of human IgG, murine C3, and the membrane attack complex of complement were found in the epidermal basement membrane of all experimental mice. Immunogold electron microscopy demonstrated that deposits of human IgG in an experimental subject were localized to anchoring fibrils. Serum samples from mice receiving IgG antibodies from our patient had high titers of circulating antibodies directed against the dermal side of 1-mol/L sodium chloride-separated human skin (titer, 640 to 1280). Light, immunofluorescence, and immunogold electron microscopic studies did not detect such specific alterations in any control mice. CONCLUSIONS: Acquired autoimmunity to type VII collagen in patients with epidermolysis bullosa acquisita may result in a clinical phenotype closely resembling that observed in patients with dystrophic epidermolysis bullosa. Passive transfer of purified IgG autoantibodies from a patient with severe epidermolysis bullosa acquisita to BALB/c mice produces histologic and immunopathologic alterations consistent with those seen in patients with this disease.

Adult↗
PubMed1998

Acquired resistance of Escherichia coli to complement lysis by binding of glycophosphoinositol-anchored protectin (CD59).

Protectin (CD59) is a glycophosphoinsitol (GPI)-anchored defender of human cells against lysis by the membrane attack complex of complement. In this study, we examined whether protectin released from human cell membranes can incorporate into the surface of gram-negative bacteria. Analysis by using radiolabeled protectin, immunofluorescence, flow cytometry, and whole-cell enzyme-linked immunosorbent assay demonstrated that protectin bound to nonencapsulated Escherichia coli EH237 (Re) and EH234 (Ra) in a calcium-dependent manner. The incorporation required the GPI-phospholipid moiety since no binding of a phospholipid-free soluble form of protectin was observed. Mg2+ did not enhance the binding, and a polysialic acid capsule prevented it (strain IH3080 [O18:K1:H8]). Bound protectin inhibited the C5b-9 neoantigen expression on complement-treated bacteria. Protection against complement lysis was observed in both a colony counting assay and a bioluminescence assay, where viable EH234 bacteria expressing the luciferase gene emitted green light in the presence of the luciferine substrate. In general, two- to four-times-higher serum concentrations were needed to obtain 50% lysis of protectin-coated versus noncoated bacteria. The results indicate that protectin can incorporate in a functionally active form into the cell membranes of the two nonencapsulated deep rough E. coli strains studied.

CD59 Antigens↗
PubMed1995

Participation of the blood platelet in immune reactions due to platelet-complement interaction.

OBJECTIVE: Review of different aspects of the primary interaction of complement with blood platelets in immunological reactions and the effect on platelet activation in healthy people and patients. DATA SOURCES AND SELECTION CRITERIA: Relevant original papers and review articles mainly of the English-written literature. RESULTS: Besides their major role in hemostasis and wound healing, blood platelets are involved in immunological reactions. They are not only able to interact with IgG through Fc receptors (FcR), they also react with complement components. This review summarizes interactions of complement with mainly human platelets. Such interactions may occur through complement receptors of the plasma membrane (e.g. C1q receptor, complement receptors 2 and 4), but also in a receptor-independent way including activation of the platelet by the membrane attack complex of complement C5b-9. In addition, activation of complement at the surface of the platelets may be induced after binding of anti-platelet antibodies to membrane glycoproteins (e.g. GpIIb/IIIa, GpIb/IX) or after binding of platelet-nonspecific immune complexes via FcR. Complement activation in turn may be regulated by various means including specific plasma or membrane proteins [e.g. decay-accelerating factor (DAF), membrane cofactor protein (MCP), membrane inhibitor of reactive lysis (MIRL), C8-binding protein (C8bp, homologous restriction factor hrf)]. As a further way of self-protection against complement attack, platelets may actively release C5b-9, deposited at the surface as C5b-9-enriched membrane vesicles. CONCLUSIONS: Two lines of interaction of platelet with complement can be distinguished. On the one hand, platelets are equipped with membrane proteins which protect them from complement attack against themselves. On the other hand, membrane receptors for activated complement components as well as for IgG are expressed on the surface, which enable the platelet to intervene in immunological reactions. This property varies between platelets of different species and needs further investigation also in view of the platelet as an intersection between immunology and hemostasis.

Antigen-Antibody Complex↗
PubMed1997

Immunohistochemical colocalization of the terminal complex of human complement and smooth muscle cell alpha-actin in early atherosclerotic lesions.

There is substantial evidence that activated components of the complement cascade are present in atherosclerotic lesions, and it was suggested some years ago that smooth muscle cells may be an important target of complement attack by the terminal components of the cascade, C5b-9, also called the membrane attack complex. Recent in vitro studies have shown that assembly of membrane attack complex on smooth muscle cells leads to the release of monocyte chemotactic protein-1, and, if this were to occur in vivo, then it could be responsible for the recruitment of monocytes into the lesion. In this study we have investigated the localization of C5b-9 in early atherosclerotic lesions of human coronary arteries, collected from autopsies, by immunohistochemical staining, C5b-9 was found to colocalize widely with smooth muscle cell alpha-actin, but not with intact macrophages, thus supporting the hypothesis that interaction of complement with smooth muscle cells may indeed be important in atherogenesis.

Actins↗
PubMed1989

Inhibition of acute passive transfer experimental autoimmune myasthenia gravis with Fab antibody to complement C6.

The role of the lytic complement C5b-9 membrane attack complex (MAC) in acute passive transfer experimental autoimmune myasthenia gravis (EAMG) produced in rats was investigated by in vivo inhibition of MAC formation with anti-C6 Fab. Anti-C6 Fab totally inhibited in vitro serum hemolytic activity, but did not consume or inhibit early complement pathways. Injection of rats with 0.12 mg/ml anti-C6 Fab reduced serum C6 to 8% and inhibited the muscle weakness, electrophysiologic abnormalities and loss of acetylcholine receptor (AChR) associated with acute EAMG. This level of C6 inhibition reduced the total serum complement hemolytic activity to 29% of normal but did not reduce the serum levels of complement components C3, C5, or C7. Treatment of rats with lower amounts of anti-C6 Fab (0.08 mg/ml) also inhibited clinical and electrophysiologic signs of EAMG, however, the lower amount of anti-C6 did not prevent the loss of muscle AChR. Both the higher and the lower amount of anti-C6 Fab inhibited the accumulation of macrophages at muscle motor end-plates. The inhibition by anti-C6 indicates that muscle weakness and electrophysiologic abnormalities associated with EAMG are dependent on the complement MAC, and that muscle weakness results from tissue injury in addition to loss of muscle membrane and AChR.

Animals↗
PubMed2003

Beyond lysis: how complement influences cell fate.

Complement is a central component of the innate immune system involved in protection against pathogens. For many years, complement has been known to cause death of targets, either indirectly by attracting and activating phagocytes or directly by formation of a membrane pore, the membrane attack complex. More recently, it has been recognized that complement may cause other 'non-classical' effects that may not directly be aimed at killing of pathogens. Products of complement activation collaborate with the adaptive immune system to enhance responses to antigens. The membrane attack complex of complement, apart from lysing cells, can also trigger diverse events in target cells that include cell activation, proliferation, resistance to subsequent complement attack and either resistance to, or induction of, apoptosis. Various complement products play important roles in signalling for clearance by phagocytes of apoptotic self cells. Here we review some of these non-classical activities of complement and stress the roles that they may play in maintaining the integrity of the organism.

Apoptosis↗
PubMed1991

Plasma terminal complement complexes in acute poststreptococcal glomerulonephritis.

In most instances of acute poststreptococcal glomerulonephritis (APSGN), activation of the complement system occurs, as reflected by decreased levels of the complement proteins C3, C5, and properdin (P). Recent studies implicate terminal complement complexes (TCC) in the pathogenesis of glomerular injury. The fluid phase TCC, SC5b-9, reflects the formation of membrane-bound C5b-9 and has been used as a clinical marker in various diseases. Plasma concentrations of SC5b-9 were measured with an enzyme immunoassay using a monoclonal antibody to a neoantigen expressed on the SC5b-9 complex in 13 children who presented with clinical and pathologic features of APSGN. SC5b-9 was significantly elevated in all plasmas obtained within 30 days after onset of clinical glomerulonephritis. Concentrations of SC5b-9 in acute plasmas were significantly higher than those of paired convalescent samples. For individual patients, as SC5b-9 concentration returned to normal there was a coincident decrease in serum creatinine concentration and urinary protein excretion, signifying clinical improvement in glomerulonephritis. Thus, TCC generation commonly occurs in the early stages of APSGN and may be of importance in the pathogenesis of the condition.

Antigen-Antibody Complex↗
PubMed1999

Identification of the individual residues that determine human CD59 species selective activity.

Formation of the cytolytic membrane attack complex of complement on host cells is inhibited by the membrane-bound glycoprotein, CD59. The inhibitory activity of CD59 is species restricted, and human CD59 is not effective against rat complement. Previous functional analysis of chimeric human/rat CD59 proteins indicated that the residues responsible for the species selective function of human CD59 map to a region contained between positions 40 and 66 in the primary structure. By comparative analysis of rat and human CD59 models and by mutational analysis of candidate residues, we now identify the individual residues within the 40-66 region that confer species selective function on human CD59. All nonconserved residues within the 40-66 sequence were substituted from human to rat residues in a series of chimeric human/rat CD59 mutant proteins. Functional analysis revealed that the individual human to rat residue substitutions F47A, T51L, R55E, and K65Q each produced a mutant human CD59 protein with enhanced rat complement inhibitory activity with the single F47A substitution having the most significant effect. Interestingly, the side chains of the residues at positions 47, 51, and 55 are all located on the short single helix (residues 47-55) of CD59 and form an exposed continuous strip parallel to the helix axis. A single human CD59 mutant protein containing rat residue substitutions at all three helix residues produced a protein with species selective activity comparable to that of rat CD59. We further found that synthetic peptides spanning the human CD59 helix sequence were able to inhibit the binding of human CD59 to human C8, but had little effect on the binding of rat CD59 to rat C8.

Amino Acid Sequence↗
PubMed1998

Glomerular deposition of mannose-binding lectin (MBL) indicates a novel mechanism of complement activation in IgA nephropathy.

BACKGROUND: IgA nephropathy (IgA-N) is considered the most common glomerular disease in the world and leads to renal failure in a substantial number of patients. Although many studies have looked at the pathogenesis of the disease, many points need to be clarified, including the mechanism of complement activation. Recent studies have shown that mannose-binding lectin (MBL or mannose binding protein, MBP) initiates activation of the complement cascade (lectin pathway) utilizing two types of MBP-associated serine protease, namely MASP-1 and MASP-2. The present study was undertaken to elucidate whether the lectin pathway was involved in the pathogenic mechanism of IgA-N. METHODS: Forty-five renal biopsy cases with IgA-N, 35 cases with other forms of glomerulonephritis (GN), and normal kidney tissues were collected and an immunohistochemical study was performed using monoclonal antibodies against MBL and MASP-1. Furthermore, clinicopathological and serological features were also analysed in the patients with IgA-N. RESULTS: Glomerular deposition of MBL, which was accompanied by MASP-1, was detected in 11 of 45 (24.4%) cases with IgA-N, while it was detected in only one case with other forms of GN. The deposited MBL/MASP-1 was observed to associate with C3b/C3c and C5b-9 but not with IgG, IgM, C1q, C4c, or properdin. Compared with MBL/MASP-1 negative cases with IgA-N, the positive cases with IgA-N were young and the renal biopsies had been performed at an early stage of the disease. No significant correlation was found between glomerular deposition of MBL/MASP-1 and proteinuria, haematuria, creatinine clearance, and serum levels of IgA, C3, or C4 at the time of renal biopsy. There were also no significant differences between MBL/MASP-1 positive cases and negative cases in the plasma levels of circulating immune complexes or soluble C5b-9. CONCLUSION: The lectin pathway of complement activation, which is initiated by the MBL/MASPs complex, evidently contributes to the development of glomerular injury in a significant number of cases with IgA-N. In addition, these findings will add insight to the pathogenesis of IgA-N, including its relation to infection, since MBL plays a crucial role in the host defense against various pathogens.

Adolescent↗
PubMed1994

Henoch-Schönlein purpura.

Henoch-Schönlein purpura (HSP) is the most common vasculitis syndrome of childhood. It is also known as anaphylactoid purpura, leukocytoclastic vasculitis, allergic vasculitis, and rarely, as rheumatoid purpura. It is generally a benign, self-limited disorder that follows an intercurrent illness, usually of the upper-respiratory tract. The classic triad of clinical symptoms and signs includes purpuric rash, abdominal cramping, and hematuria, but the spectrum of the clinical expression of HSP may vary from only minimal petechial rash to severe gastrointestinal, renal, neurologic, pulmonary, and joint disease. Most children have self-limited disease, and on long-term follow-up, systemic involvement or serious sequelae are not frequent. The current lack of knowledge about the factors underlying both the etiology and pathogenesis and the extent of clinical expression of HSP is illustrated in the recent literature. In addition, there is no agreement regarding the role of corticosteroids in the clinical management of HSP, and this subject has not received adequate attention during the past year. The recent clinical literature emphasizes the distinction between HSP and other hypersensitivity vasculitides and provides several in-depth reviews and multiple case reports illustrating the expanding clinical spectrum of the disorder. Exciting developments regarding immunologic aspects of HSP have been published and are summarized. The utility of antineutrophil cytoplasmic antibody as it applies to HSP remains to be elucidated.

Adrenal Cortex Hormones↗