Bullous pemphigoid: a correlative study of autoantibodies, circulating immune complexes and dermo-epidermal deposits

Twenty bullous pemphigoid (BP) patients were studied to establish any correlation between free anti-basement membrane zone (BMZ) antibodies, circulating immune complexes (CIC) and dermo-epidermal junction deposits. CIC levels were evaluated by 2% polyethylene glycol (PEG) precipitation. The twenty patients were found to have IgG and/or C3 deposited in the BMZ. Eight of the twelve patients who had no free anti-BMZ antibodies displayed a positive in vivo C4 and/or C_Iq staining and high levels of CIC. Moreover, CIC were detected in only one patient with positive circulating free anti-BMZ antibodies. The presence of free anti-BMZ antibodies was generally found to correlate with the absence of cutaneous deposits of C1q and/or C4 and with negative CIC; on the other hand, the absence of free anti-BMZ antibodies was generally found to correlate with high levels of CIC and with deposits of C3 and C_Iq and/or C4. The absence of circulating free anti-BMZ antibodies in BP patients, could be explained by the formation of CIC. It is possible that BMZ antigens released from damaged tissue could combine with free antibodies and form complexes in the blood. The release could involve locally formed immune complexes. Elevated CIC levels were generally found to correlate with the presence of active disease.     

Clinical significance and correlation of anti-native DNA antibodies and immune complex level in systemic lupus erythematosus.

The clinical significance and correlation of anti-native DNA antibodies and immune complex level were evaluated in the present study. Anti-DNA antibodies were measured by radioimmunoassay using I¹²⁵-labeled DNA and immune complex was screened using the polyethylene glycol precipitation method. Anti-DNA antibodies of higher than 40 units/ml were found exclusively in patients with systemic lupus erythematosus, especially in patients with lupus nephritis. The level of anti-DNA antibodies was found to be directly correlated with the disease activity. Higher amounts of circulating immune complexes could be found in patients with systemic lupus erythematosus, vasculitis, and other diseases. The patients with more active lupus erythematosus also tended to have higher amounts of immune complexes, but the correlation was not so definite. There was also no reliable correlation between anti-DNA activity and immune complex level.     

Unilateral nail dystrophy after C4 complete spinal cord injury

Summary Fifty-five patients with biopsy-proven cutaneous lupus erythematosus (LE) were identified in whom a prospective and retrospective review of the clinical and laboratory data allowed subclassification into systemic (SLE). subacute (SCLE). or discold (DLE) variants. In addition to conventional direct immunofluorescence. an indirect immunolluorescent technique. using a monoclonal antibody, was employed to assess deposition of the membranolytic attack complex (C_5b?9) in skin lesions. Deposition of C_5b?9 within the epidermis correlated with a diagnosis of SCLE with or without antibodies to Ro and was seen in SLE patients with antibodies to extractable nuclear antigens Ro. La, Sm. and RNP. and in DLE patients with positive antinuclear antibodies and/or extracutaneous manifestations. In the SLE group, vascular C_5b?9 deposition was present in six patients. Of these, tour had circulating lupus anticoagulant, one had lymphocytic vasculitis, and two had antibodies to Ro. In two patients with SLE there was keratinocyte decoration for immunoglobulin G but not for C_5b?9, in the absence of seropositivity for antibodies to Ro. La. Sm. and ribonucleoprotein (RNP). The immunohistological examination of skin lesions using a monoclonal antibody to C_5b?9 is a valuable adjunct in the subclassification of LE. The presence of C_5b?9 within skin lesions of patients with LE implies a pathogenic role for complement-mediated pore formation.     

系统性红斑狼疮(SLE)患者几项免疫指标的检测及其意义的探讨

本文报道采用LTT,EtRFCT, EaRFCT和PHA皮试对SLE患者进行细胞免疫功能测定.显示有不等程度的细胞功能低下和T淋巴细胞数的减少.体液免疫功能测定显示48多病例有IgG增高,血清ANA测定阳性串为81.1%,娥识阳性率达99.3%.滴度1≥80,病情活动者较多,斑点核型最常见.周边型、斑点线型和匀质型活动性较高.狼疮性肾病出现蛋白尿者尿ANA测定41.7%阳性.在累及中枢神经系统病例70%脑脊液ANA呈阳性.血清dsDNA间接血凝法测定29.89%阳性.¹²⁵I DNA同位索法测定结果基本上与之平行,这组病例病期较短,肾累及较多,采用PEG沉淀法测定CIC有43%增高,经解离分析CIC的主要内容为核抗原和抗核抗体复合物.CH₅₀和C₃测定有不等程度降低,最后作者对SLE的发病机理进行了讨论.     

Systemic lupus erythematosus with multiple myeloma.

A 44-year-old white man presented with an erythemato-squamous rash in the supra-orbital and preauricular regions of the face. The diagnosis systemic lupus erythematosus was confirmed by histopathology, immunofluorescence (circulating antinuclear antibodies and a positive lupus band test), and by immunoelectron microscopy. Further examinations disclosed a multiple myeloma of the IgG type without cutaneous involvement. The coexistence of these two disorders has not been reported previously.     

Elevated Serum Levels of Visfatin in Patients with Henoch-Sch?nlein Purpura

Background

Henoch-Schönlein purpura (HSP) is an immune complex-mediated disease predominantly characterized by the deposition of circulating immune complexes containing immunoglobulin A (IgA) on the walls of small vessels. Although the pathogenesis of HSP is not yet fully understood, some researchers proposed that B-cell activation might play a critical role in the development of this disease.

Objective

To investigate the serum levels of visfatin (pre-B-cell colony-enhancing factor), B-cell-activating factor (BAFF), and CXCL13, and to analyze their association with disease severity.

Methods

The serum levels of visfatin, BAFF, and CXCL13 were measured by using a double-antibody sandwich enzyme-linked immunosorbent assay (ELISA) in 43 patients with HSP and 45 controls. The serum levels of IgA anticardiolipin antibodies (ACA) were detected by using a double-antigen sandwich ELISA.

Results

Levels of visfatin but not BAFF and CXCL13 were significantly elevated in the sera of patients with HSP in the acute stage, and restored to normal levels in the convalescent stage. Furthermore, serum levels of visfatin were significantly higher in patients with HSP having renal involvement than in those without renal involvement. Serum levels of visfatin were correlated with the severity of HSP and serum concentration of ACA-IgA.

Conclusion

We show for the first time that the serum levels of visfatin are abnormally elevated in patients with HSP. Visfatin may be associated with the pathogenesis of HSP.     

Humoral immunity in stage I mycosis fungoides: an increased incidence of lymphocytotoxic antibodies

Thirteen patients with stage I mycosis fungoides (MF) were studied for the presence of circulating autoantibodies including cold-reactive lymphocytotoxic antibodies (LCA), antinuc-lear antibodies and rheumatoid factor antibodies to common food antigens, bovine gamma globulin and casein; and immune complexes as measured by cryoglobulins and I¹²⁵ Clq binding. A significantly increased incidence (11/13) of LCA was found in the MF patients, and this may be related to the alterations in subpopulations of T cells seen in these patients. No significant increase in any other test was noted. There was no evidence of a diffuse hyperactivity of the humoral immune system as seen in systemic lupus erythematosus, which has a similar imbalance of T cell subpopulations.     

Renal involvement and circulating immune complexes in dermatitis herpetiformis

A fine-needle kidney biopsy was performed on eleven patients with dermatitis herpetiformis (DH) who had no previous signs or symptoms of renal disease. Of the eight patients whose biopsy specimens were representative, electron microscopic examination showed mesangial deposits in five. A subsequent conventional renal biopsy was obtained from one of these five, and immunofluorescence microscopy revealed IgA and complement deposits in the glomeruli. Renal involvement was not related either to the degree of jejunal villous atrophy or to the deposition of IgA and complement in the skin. Glomerular deposits, however, were associated with a high frequency of circulating IgA and IgG class immune complexes and IgA class antigliadin and antireticulin antibodies. These results suggest that, in DH, immune complexes or antibodies derived from the gut can be deposited in the kidney.     

Anti-hapten antibodies and autoantibodies in Japanese patients with lepromatous leprosy

Summary In the sera of patients with lepromatous leprosy anti-DNP antibodies were detected in order to determine the mode of ployclonal B-cell activation. Anti-DNP antibodies were found in 30% of the patients with active lepromatous leprosy and in 8% of those with inactive lepromatous leprosy. The level of anti-DNP antibodies in active patients was significantly higher than the level in inactive patients and control. However, the presence of anti-DNP antibodies was unrelated to the production of circulating immune complexes and antinuclear antibodies. These results suggest that polyclonal B-cell activation might occur but that the B-cell clones stimulated by M. leprae are different from patient to patient.     

New approaches to characterizing the immune status of patients with lupus erythematosus using immunoenzyme testing

A total of 78 patients with various forms of lupus erythematosus (LE) were examined with the use of enzyme immunoassay (EIA) to test the possibility of antibody production in response to neuraminidase, an antigenic stimulant. Positive EIA results were recorded in 54.5% of patients with the integument LE forms and in 58.3% of those with systemic LE. The intensity of antibody production depended on the patients' sex (it was more active in females), age, and the disease duration. In the course of therapy negative results replace positive ones mostly in the patients with a disease of not long standing. A correlation was revealed between the content of circulating immune complexes measured by polyethylene glycol sedimentation and the levels of IgM and IgG. The detected relationship between the level of antineuraminidase antibodies and features of the disease course and therapy, agreement of this parameter with other immunologic characteristics, availability and informative value of the method recommend it for the assessment of immunity disorders in LE patients.     

Indirect complement immunofluorescence in the immunopathological assessment of bullous pemphigoid, cicatricial pemphigoid, and herpes gestationis

Sera from 50 untreated patients with bullous pemphigoid were examined by both the customary method of indirect immunofluorescence using anti IgG conjugate and by indirect complement immunofluorescence using anti C₃ conjugate to detect circulating antibasement membrane zone antibodies. A circulating antibasement membrane zone antibody could be detected by the IgG method in 58% and by the C₃ method in 76%. Sera from six patients with cicatricial pemphigoid examined in the same way showed a circulating antibasement membrane zone antibody in one by the IgG method but in three by the C₃ method of indirect immunofluorescence. Sera from ten patients with active herpes gestationis contained anti-basement membrane zone antibody demonstrable by the C₃ method in every case and by the IgG method of indirect immunofluorescence in one of these. Basement membrane zone bound IgG, or more commonly C₃ in a linear pattern, was shown by direct immunofluorescence in all patients with bullous or cicatricial pemphigoid from whom adequate biopsy material was obtained. The immunopathological similarities of bullous pemphigoid, cicatricial pemphigoid and herpes gestationis are stressed, and the usefulness of indirect complement immunofluorescence in their diagnosis is emphasized.     

Antinuclear and anti-single-stranded DNA antibodies in morphea and generalized morphea

The clinical features of localized scleroderma have allowed investigators to distinguish three morphologic variants: morphea, generalized morphea, and linear scleroderma. The latter has been reported to have a higher frequency of antinuclear antibodies and has been associated with antibodies to single-stranded DNA (ssDNA). In this study we determined the frequency of antinuclear antibodies and anti-ssDNA antibodies in 22 patients with morphea or generalized morphea. None had Raynaud's phenomenon or evidence of a systemic connective-tissue disease. Antinuclear antibodies were present in 18% of patients when serum samples were tested on mouse kidney substrate but were found in 50% of HEp-2 cells. The serum samples contained anti-ssDNA antibodies in 59% of the patients, with the highest levels of ssDNA binding observed in patients with generalized morphea. The frequency of antibodies to ssDNA was higher in patients with clinical evidence of active compared with inactive disease. Discordance in immune reactivity indicates that at least three distinctive serum autoantibodies exist in morphea and generalized morphea: anti-ssDNA antibodies and antinuclear antibodies with either homogeneous or speckled immunofluorescence patterns. These findings are similar to those recently described in linear scleroderma and suggest that comparable serum autoantibody abnormalities are present in all the variants of localized scleroderma.     

Circulating immune complexes in lupus erythematosus, scleroderma and dermatomyositis.

Circulating immune complexes (CIC) were measured by three different methods in serum from 17 patients with systemic lupus erythematosus (SLE), 3 patients with "hydralazine-induced" SLE-like syndromes, 14 patients with discoid lupus (DLE), 8 patients with systemic sclerosis and 5 patients with dermatomyositis. Immune complexes were detected in 13 of the 17 patients with SLE. All patients with lupus nephritis and typical exanthema had circulating immune complexes. The concentration of immune complexes was inversely correlated to serum complements C4 and C3. All 3 patients with "hydralazine-induced" SLE-like syndromes had circulating immune complexes that disappeared after withdrawal of the drug. Immune complexes were detected in 3 of the 14 patients with DLE; all 3 patients with CIC had wide-spread DLE. In systemic sclerosis, CIC were detected in only 1 of the 8 patients. Four of the 5 patients with dermatomyositis demonstrated CIC in serum. No complement consumption was detected in dermatomyositis and the immune complexes may have been secondary to tissue destruction.     

Silica-associated systemic sclerosis is clinically, serologically and immunologically indistinguishable from idiopathic systemic sclerosis

To determine whether the clinical, immunological and serological features of patients with silica-associated systemic sclerosis are different from patients with the 'idiopathic' form of systemic sclerosis (SS) we studied 22 underground coal miners who were exposed to silica dust (SD), 30 mine workers who later developed silicosis (S) and 17 mine workers exposed to silica dust who subsequently developed a systemic sclerosis-like disease (SA-SS). The patients with SA-SS had features clinically indistinguishable from individual patients with SS. They all had Raynaud's phenomenon, 14 had cutaneous sclerosis identical to that seen in acrosclerosis and three had a generalized cutaneous sclerosis. Sixteen patients had bibasilar pulmonary fibrosis, 10 had necrosis of the fingertip pulps, nine had oesophageal involvement and only one patient had renal involvement. Antinuclear antibodies and circulating immune complexes were detected in three and eight patients with SD, 14 and five patients with S and in 16 and nine patients with SA-SS, respectively. Anti-Scl-70 antibody was detected in eight of the 17 patients with SA-SS. Evidence for in vivo endothelial cell damage, as determined by elevated levels of von Willebrand factor, was found in nine patients with SD, 14 patients with S and in 10 patients with SA-SS. Following incubation of the patient's serum with confluent cultures of human umbilical vein endothelial cells there was only a significant reduction in calcium ionophore-induced release of prostacyclin with the serum from SA-SS patients compared to that with control serum (NC). The mean +/- SEM release of 6-keto-PGF1 alpha (the stable metabolite of prostacyclin expressed as ng/10(4) cells) decreased from 2.90 +/- 0.27 to 2.01 +/- 0.33 (SD), 3.34 +/- 0.42 to 1.76 +/- 0.31 (S), 1.98 +/- 0.12 to 0.64 +/- 0.07 (SA-SS) and 2.28 +/- 0.33 to 1.36 +/- 0.21 (NC) with 1 and 20% serum, respectively. This study demonstrates that immune complex and antinuclear antibody formation and in vivo endothelial cell damage occurs following occupational exposure to silica. The patients who subsequently develop a systemic sclerosis-like disease have clinical, immunological and serological features which are indistinguishable from the idiopathic form of the disease although as a group the SA-SS patients have a higher prevalence of pulmonary involvement and the anti-Scl-70 antibody.     

Clinical significance and correlation of antinuclear antibodies and anti-DNA antibodies.

The clinical significance and correlation of antinuclear antibodies (ANA) and anti-DNA antibodies was studied using 142 ANA positive sera from different patients having various diseases. High titers of ANA were found briefly in systemic lupus erythematosus and sometimes in scleroderma or mixed connective tissue disease. The peripheral pattern of ANA was seen exclusively in systemic lupus erythematosus and occasionally in mixed connective tissue disease. Anti-DNA antibodies could be found in systemic lupus erythematosus, discoid lupus erythematosus, scleroderma, chronic active hepatitis, but a high titer of anti-DNA (over 60 unit/ml) was present only in patients with systemic lupus erythematosus, especially those having lupus nephritis. There was little correlation between ANA and anti-DNA antibodies.     

Serum interferon in systemic lupus erythematosus

Serum interferon levels were estimated in 67 samples obtained from 47 patients with SLE. Levels were increased in 70% of the samples and 72% of the patients. In the patients with active disease 81% had increased interferon levels, while in the group with clinically quiescent disease 10% had increased levels. In 20 patients retested 3 1/2 months after treatment the changes in interferon levels tended to parallel the changes in clinical disease activity in 80% of cases. Patients with active skin lesions, arthritis, and renal or haematopoietic involvement tended especially to have increased interferon levels. Interferon levels were directly related to ANA titre and inversely related to serum C3 levels, but not related to serum levels of circulating immune complexes or immunoglobulin. The interferon was shown to be of type alpha. The interferon level can be regarded as one of several parameters reflecting disease activity and may also be related to the prognosis. As it is possible that interferon may be a direct mediator of the pathophysiology of auto-immune disease, we do not recommend the use of interferon or its inducers in the therapy of SLE.     

Immune complexes and antinuclear, antinucleolar, and anticentromere antibodies in scleroderma

Forty-one patients with various forms of systemic sclerosis (scleroderma) and positive antinuclear antibodies of nucleolar (ten patients), speckled (eleven patients), or centromere pattern (twenty patients) were selected for study of immune complexes by the radioisotope labeled Clq binding and the radioisotope labeled protein A binding methods. The presence of immune complexes was found by the Clq binding assay in sixteen patients (39%) and by a protein A binding assay in eight patients (20%). Overall, 46% of patients (19/41) had immune complexes. A lower incidence of organ involvement and fewer positive results in the screening of serum immune complexes were observed in patients with centromere antibody (35%) than in patients with nucleolar (60%) or speckled pattern (55%). Patients with immune complexes had higher frequencies of kidney, heart, and muscle involvement and digital ulceration than did patients with no detectable immune complexes, but the differences were not statistically significant. Diffuse skin involvement was not related to the presence of immune complexes.     

Nasal septum perforation as the presenting sign of lupus erythematosus

Nasal septum perforation is an uncommon and not well known feature of lupus erythematosus (LE). In general, it occurs during exacerbations and in a context of systemic vasculitis. Very rarely it can be a presenting sign, accompanying more usual manifestations of LE. We report the case of a 30-year-old woman who presented with a 2-year history of painful, slowly progressive nasal septum perforation. Laboratory study disclosed positive antinuclear antibodies, circulating immune complexes, hypocomplementemia, nuclear epidermal deposition of IgG in normal skin and transitory positive antiphospholipid antibodies. Symmetric peripheral joint arthritis, photosensitivity and diffuse alopecia subsequently developed. This case seems unique in that the nasal septum perforation occurred as an isolated presenting sign; it emphasizes the value of this feature in the diagnosis of LE.     

IMMUNOFLUORESCENCE STUDY OF DRUG-INDUCED LICHEN PLANUS-LIKE LESIONS

Using an immunofluorescence technique, we investigated lesions of drug-induced lichen planus-like lesions from patients. In addition, a comparative study of idiopathic lichen planus from thirteen patients was made. Deposits of fibrinogen along the epidermal basement zone, IgM, and less often IgA, IgG, C₁q and C3 on the colloid bodies were found in drug-induced lichen planus-like lesions. Similar deposits of immunoglobulins and complements were noted in 2 of 3 lesions developed by successful provocation tests. Deposits of fibrinogen were also demonstrated in all 3 lesions. However, no circulating antibodies directed toward the epidermal basement zone or other skin components were detected. No elevation of circulating immune complex levels was noted. Immunofluorescence findings in drug-induced lichen planus-like lesions were essentially identical to those in idiopathic lichen planus. This indicates that both conditions share a common disease process.     

Neonatal lupus erythematosus: clinical character, investigation, and outcome

Neonatal lupus erythematosus is an uncommon maternal auto-antibody-associated disease characterized by cutaneous, cardiac, hepatic, hematological, neurological, and pulmonary involvement. A retrospective study was performed to review clinical manifestations, investigation results, outcomes of neonatal lupus erythematosus patients and their mothers at the Department of Pediatrics, Siriraj Hospital during 1993 to 2008. Seventeen neonatal lupus erythematosus patients (10 girls and seven boys) were identified. Cutaneous, cardiac, hepatobiliary, and hematological involvement was found in 70.6%, 64.7%, 52.9%, and 35.3% of infants, respectively. Skin lesions were erythematous patches (91.7%), subacute cutaneous lupus erythematosus (50%), petechiae (41.7%), persistent cutis marmorata (16.7%), and discoid lesions (8.3%). Congenital heart block was found in nine cases, and structural abnormalities were found in nine cases. All sera of patients were positive for antinuclear antibodies. Patients (87.5%) showed positive antiRo/SSA, and 50% had positive antiLa/SSB antibodies. Most neonatal lupus erythematosus mothers (64.7%) were asymptomatic. Five mothers were diagnosed with systemic lupus erythematosus, and one mother was diagnosed with mixed connective tissue disease. All maternal sera was positive for antinuclear antibodies and antiRo/SSA antibody. Seven patients required pacemaker implantation. The mortality rate was 11.8%, caused by congestive heart failure and pneumonia. Antinuclear antibody tests should be used as one of the screening tests in mothers or patients suspected of having neonatal lupus erythematosus.