Deposits of Immunoglobulin and Complement in Psoriatic Lesions

Biopsy specimens from 43 patients with psoriasis were studied by immunofluorescence microscopy. Deposits of complement C3 and/or immunoglobulins were seen in the vessel walls and/or in the dermal-epidermal junction of all of 21 patients with pustular psoriasis, acute guttate psoriasis, psoriatic arthropathy and erythroderma. similar deposits were seen in nine out of 22 patients with psoriasis vulgaris. Deposits were found in clinically uninvolved skin in only one of 37 patients. The results might suggest that the deposition of immune complexes in the vessel walls are of importance for the development of psoriatic lesions.     

Cutaneous sarcoidosis: an immunofluorescence study

Biopsy specimens from granulomatous skin lesions of 14 patients with active sarcoidosis were examined by immunofluorescence microscopy. In seven lesions, deposits of IgM, IgA or complement C3 were demonstrated in the dermal vessel walls and/or at the dermal-epidermal junction. Similar deposits were found in three of twelve biopsy specimens from clinically normal skin from a buttock of the same patients. The results support the hypothesis that deposition of circulating immune complexes in the vessel walls may be of importance for the development of granulomatous lesions in sarcoidosis.     

Direct immunofluorescence in recurrent aphthous ulcers and Beh?et's disease

Direct immunofluorescence (IF) investigations in oral aphthae were performed in 17 patients with recurrent aphthous ulcers (RAU) and in 9 patients with Beh?et's disease (BD). In addition, cutaneous hyperreactivity lesions from 2 BD patients were examined. The results were compared to direct IF findings in 28 patients with nonaphthous oral diseases. There was no difference between direct IF on oral aphthae in RAU compared to BD. Deposition of C3 in vessel walls of the subepithelial connective tissue was observed in 13 of 17 patients with RAU and in all patients with BD. IgM deposits in vessel walls were found in 5 RAU and 3 BD patients. Deposition of C1q or C4 was not present. By contrast, IgG and/or IgM, C1q, C3 and C4 were detected in dermal vessel walls of skin hyperreactivity lesions from 2 BD patients. This finding is considered to be a true immune complex vasculitis. Compared to nonaphthous oral lesions, oral aphthae of BD and RAU were characterized by C3 deposition in the subepithelial vessel walls.     

Viral immune complexes in systemic lupus erythematosus: C-type viral complex deposition in skin.

Punch biopsies were examined by indirect immunofluorescence for immune complex deposits containing C-type viral antigen. Antisera specific for immunoglobulins and HEL-12 virus mediated fluorescence at the dermal-epidermal junction and in vessel walls of 16 of 16 biopsies involved skin from patients with systemic lupus erythematosus (SLE). Preimmune sera did not mediate fluorescence and gradient purified HEL-12 virus, simian sarcoma virus and baboon endogenous virus but not Rous sarcoma virus blocked the reaction of anti-HEL-12 virus serum with SLE tissue. Ten biopsies from uninvolved skin of the patients with SLE did not react with the antiviral serum, nor did tissue from 9 patients with discoid lupus erythematosus, psoriasis, bullous pemphigoid or normal skin. These data support the hypothesis that C-type viral immune complexes participate in the pathogenesis of SLE.     

Vascular changes in erythropoietic protoporphyria: histopathologic and immunohistochemical study

BACKGROUND: Erythropoietic protoporphyria (EPP) is an inherited disease caused by deficient activity of ferrochelatase in the heme biosynthetic pathway. Accumulation of protoporphyrins and light exposure results in acute phototoxic skin reactions. The histopathologic findings of the light-exposed skin are thickening of the superficial dermal vessel walls and amorphous deposits around the vessels, but the origin and detailed composition of the perivascular material have been unclear. OBJECTIVE: The vascular morphology and composition of the perivascular material were studied in the skin samples of patients with EPP. METHODS: Skin biopsy specimens of 8 patients with EPP representing 7 Finnish EPP families with different genotypes were studied by means of light and electron microscopy and immunohistochemical methods. RESULTS: The characteristic finding was thickened, periodic acid-Schiff-positive vessel walls caused by concentric reduplication of basal lamina and excess of fine granular material at the basal membrane zone in the superficial dermis. The perivascular deposits in the vicinity of vessel walls had a homogeneous or fine granular appearance without filaments. Direct immunofluorescence showed constant IgG deposits together with IgA, IgM, and C3 in the vessel walls. In immunohistochemistry, collagen IV and laminin could be demonstrated at the vascular basal membrane together with serum amyloid P protein, kappa and lambda light chains, and a 90-kd glycoprotein. CONCLUSION: The vascular involvement indicates that the blood vessel walls in the papillary dermis are the primary tissues affected during an acute photoreaction. The repeated acute damage and repair processes in the basement membrane zone result in thickening of the vessel walls. Perivascular deposits are a secondary and irreversible phenomenon resulting from the leakage and accumulation of different serum components. These changes were not found in the nonexposed skin, indicating that an increased level of erythrocyte protoporphyrin per se is not responsible for the cutaneous manifestations, but the interaction of solar radiation is mandatory. Amorphous deposits distinguish EPP from variegate porphyria and porphyria cutanea tarda; a histopathologic examination may be a helpful tool in differentiating porphyric and nonporphyric photosensitivity.     

Co-localization of IgA and TG3 on healthy skin of coeliac patients

BACKGROUND: Dermatitis herpetiformis (DH), the skin's expression of coeliac disease (CD), is induced by the presence of IgA antibodies and epidermal transglutaminase (TG3) as the main autoantigen, stored in the papillary dermis and on the vessel walls. AIMS: To evaluate the presence of IgA and TG3 deposits, considered to be the first step in inducing DH, in healthy skin of coeliac patients without cutaneous manifestations. METHODS: Punch biopsies were taken from 11 consecutive coeliac patients, two with DH and nine without cutaneous manifestations, three of whom were adhering to a gluten-free diet (GFD), and evaluated for the presence of deposits in the upper dermis and vessel walls by immunofluorescence and confocal microscopy. RESULTS: In coeliac patients affected by DH we found the presence of IgA and TG3 deposits mainly on the upper dermis, but also in vessel walls. In all coeliac patients without DH and also in those patients who were following a strict GFD, we found widely variable deposits of IgA and TG3 in both the papillary dermis and the vessel walls, although a lower intensity of the fluorescence signal was detected than with coeliac patients affected by DH. Double immunostaining with anti-IgA and anti-TG3 antibodies showed a strong co-localization in the upper dermis in patients with DH and a weaker co-localization in those without DH. CONCLUSIONS: We have demonstrated the presence of IgA and TG3 deposits in the healthy skin of coeliac patients, which are considered to play a central role in the pathogenesis of DH.     

Immunofluorescence Studies in Scabies

Direct and indirect immunofluorescence investigations performed for 11 patients with scabies. All patients had punch biopsies taken from (1) a lesion containing Sarcoptes scabiei, (2) an inflammatory papule which did not contain a mite, and (3) normal skin. In four patients IgE deposits were found in the vessel walls of the upper dermis both in biopsies containing mits and biopsies of inflammatory papules with no mites. No IgE deposits were found in biopsies of normal skin from the same patients. Two patients had IgM and/or C3 deposits along the basal membrane in biopsies containing mites and one of them also had C3 in this area in the biopsy from a papule with no mite, as well as normal skin.     

Pityriasis lichenoides, an immune complex disease?

Nine biopsies from skin lesions of 5 patients with pityriasis lichenoides acuta and three biopsies from skin lesions of 3 patients with pityriasis lichenoides chronica were examined by means of the direct immunofluorescence technique. IgM deposits along the dermoepidermal junction were found in only two biopsies. In the majority of bioipsies, complement (C3) deposits were found along the dermo-epidermal junction and in the vessel walls. Immunoglobulin and C3 deposits were not found concomitantly in the vessel walls.     

Immunofluorescent studies of the skin in mixed cryoglobulinaemia and Sch?nlein-Henoch purpura.

Immunofluorescence investigations in patients with mixed cryoglobulinaemia, Sch?nlein-Henoch purpura and purpuric allergic reaction with disseminated intravascular coagulation have been performed. In the lesional skin from 8 patients with mixed cryoglobulinaemia, granular vascular deposits of immunoglobulins of the same classes as those of the circulating cryoglobulins were detectable in all cases; complement and fibrinogen were concomitantly present. In the unaffected skin, IgM and complement were detected in the walls of the capillaries. In the early purpuric lesions from 6 patients with Sch?nlein-Henoch syndrome and from a patient with diseeminated vascular coagulation from acute allergic reaction to phenylbutazone, deposits of fibrinogen occurred mainly in the vessel walls.     

Deposits of complement and immunoglobulins in vessel walls in pyoderma gangrenosum

Previous immunofluorescence studies on pyoderma gangrenosum (PG) proved negative. Biopsies from the ulcer edge of 8 patients with PG were examined by immunofluorescence microscopy. Deposits of complement C3 were seen in the vessel walls of all samples, IgM in three and IgA in one. Granular deposits of C3 were seen at the dermal--epidermal junction in 2 patients. Biopsies from clinically normal skin of 6 of the patients were negative. It is suggested that deposition of immune complexes in the dermal vessel walls may play a role in the pathogenesis of PG.     

Deposits of immunoglobulins and complement in the dermoepidermal junction of patients with anaphylactoid purpura.

Skin biopsies from 3 patients with anaphylactoid purpura examined by an immunofluorescence technique revealed deposits of immunoglobulins, complement C3, and fibrinogen in the dermo-epidermal junction and in vessel walls of clinically involved as well as uninvolved skin. The deposits in the dermo-epidermal junction are similar to those seen in the skin of patients with systemic lupus erythematosus.     

Demonstration of circulating and tissue-fixed immune complexes in cutaneous necrotizing vasculitis

Simultaneous demonstration of circulating and tissue-fixed immune complexes was attempted in 22 patients with cutaneous necrotizing vasculitis (7 anaphylactoid purpura, 9 cutaneous allergic vasculitis, 2 livedo reticularis, 1 thrombophlebitis, 2 erythema elevatum diutinum and 1 acute generalized pustular bacterid). In 16 out of the 22 patients, particularly patients with anaphylactoid purpura and cutaneous necrotizing vasculitis, there was a high Clq-binding activity. Decreased levels of C3 and C4 were seen in 2 and 3 patients, respectively. In 11 out of 16 skin lesions, the granular deposits of immunoglobulins and/or complement were demonstrated in the blood vessel walls of the dermis. IgA deposit was seen in anaphylactoid purpura, and IgM deposit in other types of vasculitis. C3 deposit was the most frequently noted. There was no definite correlation between Clq-binding activity and tissue deposits.     

Leukocytoclastic vasculitis - correlation between different histologic stages and direct immunofluorescence results

Background Leukocytoclastic vasculitis is a well-known clinico-pathologic entity. A good correlation between clinical and direct immunofluorescence (DIF) findings has been shown only in the early stages of vasculitis. Our purpose was to determine the correlation between different stages of vasculitis, etiology of vasculitis, and DIF findings. Methods Histologic and DIF studies were performed and evaluated from 40 patients with leukocytoclastic vasculitis. Results Thirty-seven out of 40 patients (92%) showed positive DIF findings in the blood vessel walls. Eight patients were in the early stage of vasculitis and exhibited deposits mainly of fibrinogen, C3, and IgM. Seventeen patients were at the fully developed vasculitis stage and showed albumin, fibrinogen, and IgG deposits. Fifteen patients were in the late stage of vasculitis and showed deposits of mainly fibrinogen and C3 in the blood vessel walls. Conclusions The present study demonstrates that DIF examination is a very sensitive test in the diagnosis of vasculitis, and can be used in all stages of vasculitis and not only in the early stages as has been shown in previous studies.     

Demonstration of immune complexes in spontaneous and histamine-induced lesions and in normal skin of patients with leukocytoclastic angitis.

Clinical and laboratory observations have strongly suggested that leukocytoclastic angitis is an immune complex disease. Since immune complexes can be visualized as electron-dense deposits by electron microscopy (EM), this method was used in conjunction with direct immunofluorescence (IF) to determine whether complexes could be demonstrated in spontaneous lesions, and in uninvolved skin in which the vessels were made permeable by the local injection of histamine. Histamine-induced wheals were produced in the uninvolved skin of patients with active angitis. In the resulting wheal, EM studies revealed electron-dense deposits characteristic of immune complexes in postcapillary venules and direct IF studies demonstrated complement and immunoglobulins in the vessel walls. Neutrophils in varying stages of disintegration were present thereby reproducing the histopathologic changes of spontaneous lesions. EM and IF studies of nonmanipulated uninvolved skin also revealed electron-dense deposits and immune reactants in the vessel walls. Neutrophils were not present, however. This observation indicates that immune complexes are deposited in vessels before tissue damage ensues. Study of spontaneous lesions older than 24 hr revealed only fibrin by EM and no immune reactants by direct IF. In spontaneous lesions less than 24 hr old, electron-dense deposits and fibrin were seen by EM, and complement and immunoglobulins by IF. Histamine-induced wheals should be a useful device to investigate patients with disorders that have an immune complex pathogenesis.     

Immunoglobulin and complement deposits in the skin and circulating immune complexes in scabies

Sixteen patients with papulovesicular, 6 with nodular and one with a Norwegian scabies were studied. Direct immunofluorescence (IF) examination revealed C3 deposits in the skin lesions of 13 of the 18 patients. Among them were all 6 cases with nodular scabies. C3 was found mostly in dermal vessel walls and 3 of the patients also showed IgM and 2 IgA deposits at the same site. No circulating immune complexes were found, with a solid-phase C1q radioimmunoassay (RIA), but HSV- and RSV-RIA methods detected IgM antibodies of rheumatoid factor type in 5 of the 15 sera examined. These results suggest that local complement activation and perhaps also immune complex deposition may by important in the pathogenesis of the papular and nodular skin lesions of human scabies.     

Membrane attack complex of complement in Henoch-Schönlein purpura skin and nephritis

Summary The present study using direct immunofluorescence with monoclonal antibodies to C5b-9 complex-related antigens was undertaken to determine whether complement activation in Henoch-Schönlein purpura (HSP) causes assembly of the membrane attack complex of complement (MAC) in skin and nephritis lesions. The deposition of C5, C6, C7, C8, C9, and C5b-9 neoantigens was noted in the vascular walls of papillary dermis and/or subpapillary dermal plexus of the vessels in 11 out of 15 patients with HSP. Their presence in vessel walls indicates complement activation which leads to terminal complement activation. There were small deposits of S protein at the same sites in three of the 11 skin specimens. Thus, the majority of C5b-9 demonstrated in HSP skin was the cytolytically active C5b-9 complex, MAC. Granular deposits of C5b-9 related antigens without S protein were also found in the capillary walls and mesangium of the glomeruli of two out of four specimens from patients with HSP nephritis; in the other two S protein was colocalized with the deposition of C5b-9. The results of the present study indicate that complement activation leading to generation of MAC may possibly be involved in the pathogenesis of vascular injury in a significantly large number of skin lesions and of HSP nephritis.     

Pyoderma gangrenosum and leucocytoclastic vasculitis in association with rheumatoid arthritis—a report of two cases

Although pyoderma gangrenosum and leucocytoclastic vasculitis are both well-recognised complications of rheumatoid arthritis, there have been surprisingly few reports of the two disorders occurring together. We have recently investigated two patients with this association and have demonstrated deposits of IgM, IgA, C₃ and fibrinogen in the blood vessel walls of what were clinically typical pyoderma gangrenosum-like lesions.     

寻常型银屑病患者血管内皮生长因子及单核细胞趋化因子-1表达的研究

目的 探讨血管内皮生长因子(VEGF)、单核细胞趋化因子-1(MCP-1)在银屑病患者皮肤中的表达及其意义。方法 用免疫组化法检测银屑病患者皮损、非皮损及正常人皮肤中VEGF、MCP-1的表达与分布。用双抗体夹心酶联免疫吸附法检测患者血清中VEGF、MCP-1水平。结果 ①银屑病患者皮损及非皮损中VEGF表达较正常人皮肤明显增强(P<0.05).皮损中MCP-1表达较非皮损及正常人皮肤明显增强(P<0.05).②患者血清中VEGF水平明显高于正常人(P<0.05),MCP-1水平与正常人比较差异无显着性(P>0.05).③皮损角质形成细胞中VEGF、MCP-1的表达与PASI评分无显着相关性(P>0.05)。结论 VEGF、MCP-1的表达增强在银屑病的发病机制中可能起重要作用。     

Immune deposits in cutaneous lesions of Wegener's granulomatosis: predictor of an active disease

A retrospective analysis was conducted of eight cases of Wegener's granulomatosis (WG), who presented with cutaneous lesions. The clinical, immunopathologic and histopathologic features of the cutaneous lesions were reviewed. Antineutrophil cytoplasmic antibody (ANCA) status of the patients was established. When possible, a comparison of immunofluorescence findings of skin biopsies was made with those of renal biopsies taken at the same time. In all except one, systemic and cutaneous disease developed concurrently. On histopathology, leukocytoclastic vasculitis was noted in five patients and features of lupus erythematosus and pyoderma gangrenosum in one case each. Four patients showed immunoglobulin deposits in subepidermal blood vessel walls, while one patient showed granular immune deposits at dermo-epidermal junction only. Immunoglobulin G was the most common immunoreactant detected. C-ANCA/proteinase 3 (PR3)-ANCA was positive in six patients, P-ANCA/myeloperoxidase (MPO)-ANCA in one patient, while one patient did not show ANCA positivity on indirect immunofluorescence. All four renal biopsies showed pauci-immune glomerulonephritis, irrespective of the presence (n=3) or absence (n=1) of immune deposits in the skin biopsy. Skin manifestations are encountered in nearly half of the patients with WG, thus it is important to be familiar with cutaneous histopathologic as well as immunofluorescence findings in WG patients.     

Psoriasiform eruption induced by propranolol.

The appearance of a psoriasiform eruption in a seventy-eight year old patient after one year of treatment with propranolol is presented herein. The histologic picture was not compatible with psoriasis vulgaris, although it contained some of the same features. Immunologic investigation revealed immune deposits at the junction of the dermis and epidermis and in blood vessel walls as well as monoclonal gammopathy. The rash, which was followed by a reduction in tear secretion, is suggested to have been a drug reaction associated with propranolol. This is supported by the positive results of a migration inhibiting factor test towards propranolol, the clearing of the eruption which took place three weeks after withdrawal of the drug, and the negative result of the same test obtained soon afterwards.