A nonrandomized comparison of the clinical outcome of ocular involvement in patients with mucous membrane (cicatricial) pemphigoid between conventional immunosuppressive and intravenous immunoglobulin therapies

The purpose of this study was to compare the clinical outcomes of intravenous immunoglobulin (IVIg) therapy to conventional immunosuppressive therapy in patients with mucous membrane pemphigoid (MMP), also known as cicatricial pemphigoid (CP), whose disease progressed to involve the eye. Before ocular involvement, all the patients in this study were diagnosed and treated with immunosuppressive agents, for biopsy-proven MMP, affecting the skin and/or mucous membranes, other than the conjunctiva. Eight patients in group A were treated with IVIg after the diagnosis of ocular cicatricial pemphigoid (OCP) was established. The efficacy and safety of IVIg therapy were compared to a clinically similar group of eight patients treated with conventional immunosuppressive therapy (group B). The inclusion criteria for both groups were: (1). presence of MMP at extraocular sites confirmed by biopsy before entry into the study; (2). entry into the study occurred when ocular involvement was noted and confirmed by biopsy; (3). presence of conventional immunosuppressive therapy at the time of ocular involvement; (4). a minimum of 18 months of follow-up after diagnosis of ocular involvement. The mean length of the therapy, after the onset of ocular involvement, was 24 months (range 16-30) in group A and 45 months (range 21-90) in group B. The median time between initiation of therapy and clinical remission in group A and group B was 4 and 8.5 months, respectively. This difference was statistically significant (P < 0.01). No recurrence of ocular inflammation was recorded in any of the patients in group A. On the contrary, at least one recurrence (median 1) was recorded in five patients in group B (range 0-4). This difference was statistically significant (P < 0.05). All eight patients in group A and group B presented to the ophthalmologist in stage 2 of OCP at the time of the initial visit. At the last follow-up visit, no progression to advanced stages of OCP was recorded in all eight patients in group A. On the contrary, only four patients in group B remained in stage 2 of OCP at the last follow-up exam. The conjunctival scaring progressed from stage 2 to stage 3 in the remaining four patients of group B. At the last follow-up visit, both eyes of each patient in group A were free of inflammation. Some level of conjunctival inflammation at the last follow-up visit was noted in five patients in group B (range 0-1.5, P < 0.05). Both groups of patients were studied during the same time period. The results of this study suggest that ocular involvement in patients with MMP may be considered an indication for initiating IVIg therapy, since it was more effective in arresting progression of OCP, when compared to conventional immunosuppressive therapy. These data indicate that IVIg produced a faster control of the acute inflammation and that no recurrences were observed during the follow-up. This clinical difference could be because of the reduced production of pathogenic antibody, and/or restoration of the immunoregulation, which may have been disturbed.     

Intravenous immunoglobulin therapy in patients with multiple mucosal involvement in mucous membrane pemphigoid.

Mucous membrane pemphigoid (MMP), also known as cicatricial pemphigoid (CP), is an autoimmune mucocutaneous, blistering disease which can lead to blindness and/or death from sudden asphyxiation, secondary to a scarring process. Conventional therapy for the treatment of MMP consists of high-dose systemic corticosteroids and/or immunosuppressive agents. Some patients do not respond to these treatments and develop multiple serious side effects, which can be potentially fatal. In such patients, alternative treatment modalities are needed. This study presents the use of intravenous immunoglobulin (IVIg) therapy in 15 patients with severe MMP whose disease was nonresponsive to the prolonged use of high-dose systemic corticosteroids and immunosuppressive agents and who developed multiple side effects to them. All 15 patients received an IVIg dose of 1-2 g/kg/cycle. The following objective parameters were used to assess the clinical outcome pre- and post-IVIg therapy: number of side effects, frequencies of recurrences and relapses, duration and total dosage of prednisone therapy, and the quality of life. The differences in these variables between the pre- and post-IVIg data were statistically analyzed using the SAS UNIVARIATE software running the two-sided Wilcoxon signed-rank and sign tests. A statistically significant difference was observed between pre- and post-IVIg therapy data when comparing the aforementioned variables. All 15 patients had an effective clinical response, were able to discontinue previous systemic therapies, and eventually achieved a prolonged clinical remission. IVIg improved the quality of life in all 15 patients and demonstrated a steroid-sparing effect. No serious side effects were observed. IVIg therapy is a safe and effective alternative modality in the treatment of patients with nonresponsive and progressive MMP and can induce a sustained clinical remission.     

Pemphigus and mucous membrane pemphigoid: An update from diagnosis to therapy

Pemphigus diseases (PDs) and mucous membrane pemphigoid (MMP) are a group of immune-mediated mucocutaneous disorders clinically characterized by the formation of blisters, erosions and ulcers. The skin and mucous membranes are predominantly affected, with the oropharyngeal mucosa as the initially involved site. Ocular involvement is also a frequent feature of these diseases. Because of the considerable overlap in their clinical presentations, the diagnosis of PDs vs. MMP can be challenging. A recognition of their specific immunological and histopathologic features is crucial in the differential diagnosis. Treatment modalities include systemically administered corticosteroids, steroid-sparing immunosuppressive agents, and biologic therapies (rituximab, intravenous immunoglobulins, and anti-tumor necrosis factor agents). Topical, oral, conjunctival, or intralesional corticosteroids as well as anti-inflammatory drugs and antibiotics are prescribed as needed.     

钙调神经蛋白在抗肾小球基底膜病肾小球内的表达增强

 目的 观察抗肾小球基底膜（GBM）病患者肾小球足细胞钙调神经蛋白（CaN）的表达,了解其与临床病理特点及肾脏长期存活的关系。方法 选取临床病理资料完整的抗GBM病患者29例,对照为8例肾小球轻微病变患者。收集患者临床资料,免疫组化方法检测CaN A亚基α亚单位（CnAα）在肾小球的表达,免疫荧光染色观察足细胞骨架蛋白synaptopodin表达,分析CnAα与临床病理表现及预后的关系。结果 29例抗GBM病患者肾小球内均有不同程度的CnAα表达阳性,阳性区域占肾小球面积百分比显著高于轻微病变者（21.63%±14.27% vs 2.21%±1.41%,p<0.01）,同时伴有synaptopodin缺失。CnAα的表达量与抗GBM抗体峰值、血肌酐水平、血红蛋白水平、新月体比例及细胞/细胞纤维新月体比例呈现显著相关性,并与预后相关。结论 首次观察到抗GBM病患者肾小球内CnAα表达增强,表达量与疾病活动、严重程度及预后相关,提示足细胞可能参与抗GBM病新月体形成,其作用机制仍有待进一步研究。     

Immunohistochemical distributions of cathepsin B and basement membrane antigens in human lung adenocarcinoma: association with invasion and metastasis

The distributions of cathepsin B (CB) a lysosomal cysteine proteinase, type IV collagen (CIV) and laminin (LM), which are main components of basement membranes (BMs) were studied in a series of 64 human lung adenocarcinomas using an immunohistochemical technique. Over-expression of CB (>80% positive cells) was significantly associated with the grade of tumour differentiation (p<0.01), with lymph node metastasis (p<0.01) and with BM degradation (p<0.01) detected by the staining pattern of CIV and LM. It was significantly associated with a prognostic disadvantage (p<0.01). The immunohistochemical staining pattern of CB has a close relationship with degradation of BM, and may be used as a marker for tumour metastasis and prognosis in lung adenocarcinoma.     

IVIg therapy in autoimmunity and related disorders: our experience with a large cohort of patients

Intravenous immunoglobulin (IVIg) is used to treat a number of immune-deficiencies and autoimmune diseases. It has been shown that IVIg contains anti-idiotypic antibodies, which explains its immunomodulatory action.

In murine models, recent investigations have demonstrated that IVIg can prevent and reduce the affliction by systemic lupus erythematosus (SLE), antiphospholipid syndrome (APS) and scleroderma. Relevant disease-specific fractions of IVIg were able to reproduce and even enhance the therapeutic effect in a murine model.

IVIg treatment before tumor resection in rodents inoculated with melanoma and sarcoma cells dramatically improved the cure rate (50%) in comparison to the control group (0%).

In patients affected by SLE, several clinical manifestations responded to IVIg treatment including serositis, hematological manifestations, treatment-resistant nephritis and central nervous system involvement. Similarly, in women with recurrent fetal loss due to APS, IVIg was able to diminish the abortion rate. Vasculitides such as Churg–Strauss' and Wegener's and skin fibrosis in patients affected by scleroderma improved after IVIg treatment. In agreement with in vitro investigations, prolonged survival has been noted in cancer patients treated with IVIg.

We suggest that in the presence of a steroid and immunosuppressive-resistant autoimmune disease, IVIg is a rational and safe choice.     

Specific alterations of the basement membrane and stroma antigens in Human pituitary tumours in comparison with the normal anterior pituitary. An immunocytochemical study

Summary Our report is the first immunocytochemical study of the principal elements of the basement membrane (BM) and connective tissue in normal and adenomatous human anterior pituitaries. In normal tissues, both the parenchymatous BM limiting the endocrine cell cords and the endothelial BM around the capillaries were continuous and were stained with anti-laminin (LM), anti-type IV collagen (CIV) and anti-fibronectin (FN) antisera. Antiserum to type I collagen (CI) stained the connective tissue only. The same antigens were investigated in 23 human pituitary adenomas, 6 of them having been diagnosed as locally invasive by the radiologist and the neurosurgeon. In all cases a lack of cordai structure was observed and the parenchymatous BM was completely absent (9 cases) or fragmented (14 cases). No correlation could be established between the extent of parenchymatous BM alterations and the invasive behaviour of the tumour. In contrast, a continuous endothelial BM was observed around the blood vessels in all cases and its presence was confirmed in double immunofluorescence experiments using anti-von Willebrand factor and anti-LM or anti-CIV antisera. Anti-FN and CI also stained the wall of the vessels. The tumours showed arterial development, in addition to the capillaries found in normal tissue. The present results favour the hypothesis of a decreased synthesis of parenchymatous BM by human adenomatous pituitary cells in comparison with normal cells and show that these tumours are the site of an active arterial neovascularization.     

Spin labeling studies of membrane proteins in erythrocyte ghosts from patients with Huntington's disease

Previous electron spin resonance (ESR) studies employing a protein-specific spin label have suggested an alteration in membrane proteins in erythrocytes in Huntington's disease (HD). Recently, Beverstock and Pearson [4] have published the results of an ESR study not confirming our findings. In the present communication, we show that with correct use of the statistical technique of the Dixon test to determine if extreme values can be eliminated, one of the data points of these authors can be rejected. Recalculation of their results suggests a significant difference in the physical state of membrane proteins in HD erythrocytes, confirming our findings.     

Alteration of the basement membrane in human thyroid diseases: An immunohistochemical study of type IV collagen,laminin and heparan sulphate proteoglycan

Basement membrane (BM) alteration in thyroid diseases was examined by immunohistochemistry using antibodies for the three major BM proteins: type IV collagen, laminin and heparan sulphate proteoglycan. Linear epithelial BMs surrounding follicles accompanied by vascular BMs forming loops, similar to those seen in the normal thyroid, were observed in Graves' disease and adenomatous goitre. Hashimoto's thyroiditis showed scant epithelial BMs as a result of follicle destruction. In follicular adenomas, development of epithelial BMs seemed to be related to follicle formation; well-developed epithelial BMs were frequently seen in normo- or largefollicular type, whereas trabecular or solid types revealed scant or poorly developed epithelial BMs. Lumpy accumulation of BM proteins was detected in hyalinizing trabecular adenomas. Papillary carcinomas revealed two different types of papillae; one type contained both epithelial and vascular BMs, and the other had only vascular BMs. Epithelial BMs in invasive areas of papillary carcinoma were distributed in an irregular, interrupted manner, and were completely absent in many foci. Anaplastic carcinomas showed scant or a total loss of epithelial BMs. These results suggest that alterations of BM in thyroid diseases clearly reflect their architectural variations, presumably in connection with their function and/or biological behaviour.     

Efficacy and long-term follow up of combination therapy with interferon alpha and ribavirin for chronic hepatitis C in Korea

Combination therapy with interferon alpha (IFN-alpha) and ribavirin for 24 or 48 weeks according to HCV genotype has improved the overall sustained virological response (SVR) rates to approximately 40%. The aim of this study was to investigate the long-term efficacy of combination therapy with IFN-alpha and ribavirin for chronic hepatitis C in Koreans. One hundred thirty-eight patients with chronic hepatitis C who received this combination therapy between 1995 and 2003 were analyzed retrospectively. All patients were treated with IFN-alpha 3-6 million units three times weekly in combination with 900-1200 mg/day of ribavirin for 24 weeks. The overall SVR rate was 41.3%. Patients were followed up for a median of 41 months (range, 12-105 months) after completion of therapy. In all of the SVR patients (57 patients), SVR was conserved during the follow-up period. None of the patients progressed to decompensated liver disease or hepatocellular carcinoma (HCC). However, 5 of the 81 non-SVR patients (6.2%) progressed to decompensated liver disease or HCC. In conclusion, combination therapy with IFN-alpha and ribavirin shows good long-term efficacy in patients with chronic hepatitis C in Korea, one of the highest endemic areas of hepatitis B virus (HBV) infection.     

糖尿病合并冠心病患者红细胞膜脂肪酸成分改变与胰岛素抵抗

我们采用高效液相色谱（PHLC）和荧光偏振技术测定了2型糖尿病合并冠心病病人红细胞膜脂肪酸成分和膜微粘度,并分析了脂肪酸成分、膜流动性和胰岛素敏感指数（ISI）与冠心病发生的关系。结果表明糖尿病人红细胞膜花生四烯酸（AA,C20：4）含量及组成明显低于对照组,而伴冠心病组AA含量又低于单纯糖尿病组,且其总脂肪酸含量明显低于对照组。两组病人膜微粘度明显高于对照,而冠心病组又明显高于单纯糖尿病组。糖尿病人红细胞膜AA含量与膜微粘度呈负相关,与ISI呈正相关,膜微粘度与ISI呈负相关。AA含量,微粘度和ISI均与冠心病的发生有关。提示糖尿病人冠心病的发生、发展与其脂肪酸代谢紊乱有关。     

Immunological and clinical profile of adult patients with selective immunoglobulin subclass deficiency: response to intravenous immunoglobulin therapy

Selective immunoglobulin (Ig)G3 subclass deficiency in adults, especially its immunological profile, has not been described previously in detail. Therefore, a retrospective chart review was conducted to characterize the immune profile and clinical manifestations in adult patients with selective IgG3 deficiency. We reviewed the charts of 17 adult patients attending our subspeciality immunology clinic with a diagnosis of selective IgG3 deficiency. The following immunological test results were recorded: lymphocyte subsets, proliferative response to mitogens (phytohaemagglutinin, concanavalin A, pokeweed mitogen) and soluble antigens (mumps, Candida albicans, tetanus toxoid), specific antibody response to tetanus toxoid and pneumococcal antigens, neutrophil oxidative burst and natural killer cell cytotoxicity. In addition, we recorded information about the types of infections and other associated diseases, and response to intravenous immunoglobulin therapy (IVIG). In the majority of patients, lymphocyte subsets were normal. Proliferative responses to mitogens and antigens were decreased in 33% and 40% of patients, respectively. Specific antibody responses to tetanus were normal; however, responses to various pneumococcal serotypes were impaired in a subset of patients. Patients suffered from recurrent upper respiratory tract infections, which usually decreased in frequency and severity following treatment with IVIG. The majority of these patients also had concurrent atopic diseases in the form of allergic rhinitis or asthma. Selective IgG3 subclass deficiency should be considered in adults with recurrent upper respiratory tract infections with or without allergic rhinitis or asthma, who may have normal levels of total IgG. IVIG appears to be an effective therapy.     

Distinctive characteristics of bronchial reticular basement membrane and vessel remodelling in chronic obstructive pulmonary disease (COPD) and in asthma: they are not the same disease

Soltani A, Muller H K, Sohal S S, Reid D W, Weston S, Wood‐Baker R & Walters E H
(2012) Histopathology  60, 964–970 Distinctive characteristics of bronchial reticular basement membrane and vessel remodelling in chronic obstructive pulmonary disease (COPD) and in asthma: they are not the same disease Aims: This study compared reticular basement membrane (Rbm) and vascular remodelling within the bronchial mucosa of subjects with chronic obstructive pulmonary disease (COPD) with those from patients with asthma, to test the ‘Dutch hypothesis’ of whether these are essentially the same or different pathological conditions. Methods and results: Bronchoscopic biopsies were stained with anti‐collagen IV antibody; 18 current smoking COPD, 10 symptomatic asthmatics and 13 healthy non‐smoking controls were studied. The Rbm in COPD was fragmented, non‐homogeneous, variable in thickness and hypervascular, whereas in asthma the Rbm was compact and homogeneous with no evidence of increased vascularity compared to controls. Length of Rbm splitting presented as percentage of Rbm length was used to measure fragmentation; it was greater in COPD than in controls and asthmatics [median (range) 20.7% (0.4–68.5) versus 5.3% (0.0–21.7) versus 1.5% (0.0–15.1), P < 0.001]. The number of Rbm vessels/mm Rbm [median (range) 10.1 (1.6–23.0) versus 4.5 (0.0–26.4) versus 4.4 (0.4–8.1), P < 0.01] and area of Rbm vessels, μm²/mm Rbm [median (range) 953 (115–2456) versus 462 (0–3263) versus 426 (32–2216), P < 0.05] was also increased in COPD compared to normal subjects and asthmatics. Conclusions: The characteristics of Rbm remodelling are quite different in asthma and COPD.     

Cross-reaction between Yersinia outer membrane proteins and anti-Borrelia antibodies in sera of patients with Lyme disease

Diagnosis of Yersinia infections accompanied by reactive arthritis could be complicated by cross-reaction with other arthritogenic bacteria. The possible cross-reaction between Yersinia antigens and anti- Borrelia antibodies in blood sera of patients with Lyme disease was studied. The occurrence of specific IgA, IgG and IgM antibodies was analyzed in serum samples from 30 patients with Yersinia -triggered reactive arthritis, 30 patients with Lyme disease and five samples from healthy blood donors. For anti- Borrelia IgG antibodies, cross-reaction was detected with YopH, YopB, V-ag, YopD, YopN, YopP and YopE, and for IgA with YopD. For IgM, no cross-reaction was detected. Owing to cross-reactivity with Borrelia , the diagnosis of Yersinia -triggered reactive arthritis should be based on a combination of serological and clinical findings.     

The evolution of crescentic nephritis and alveolar haemorrhage following induction of autoimmunity to glomerular basement membrane in an experimental model of Goodpasture's disease

Goodpasture's, or anti-glomerular basement membrane (GBM), disease presents with rapidly progressive glomerulonephritis and lung haemorrhage, and is caused by autoimmunity to the NC1 domain of the alpha3 chain of type IV collagen (alpha3(IV)NC1). This study examines the development of crescentic nephritis and alveolar haemorrhage in a model of Goodpasture's disease, experimental autoimmune glomerulonephritis (EAG), induced in WKY rats by immunization with rat GBM in adjuvant. An increase in circulating anti-GBM antibodies and albuminuria was observed by week 2, which increased further by weeks 3 and 4, while a decrease in creatinine clearance was observed by week 2, which decreased further by weeks 3 and 4. The kidneys of animals with EAG showed linear deposits of IgG on the GBM and a transient glomerular infiltration by CD4+ T cells at week 2. By week 3 there were large deposits of fibrin in Bowman's space, and glomerular infiltration by CD8+ T cells and macrophages, accompanied by focal necrotizing glomerulonephritis with crescent formation. Ultrastructural studies showed glomerular endothelial cell swelling and epithelial cell foot process effacement at week 2. As the lesion progressed, capillary loops became occluded and the mesangium became expanded by mononuclear cells. By week 3 there was detachment of the endothelium from the GBM, and accumulation of fibrin beneath the disrupted endothelial cells and in Bowman's space. Occasional breaks were observed in the continuity of the basement membrane, and cytoplasmic projections from infiltrating mononuclear cells could be seen crossing the capillary wall between the lumen and the crescent. The lungs of animals with EAG showed patchy binding of IgG to the alveolar basement membrane (ABM) at week 2, and infiltration of the interstitium by CD8+ T cells and macrophages by weeks 3 and 4, accompanied by both interstitial and alveolar haemorrhage. Ultrastructural studies showed focal mononuclear cell infiltrates in alveolar walls at week 2. Occasional breaks were observed in the basement membrane and adjacent endothelium by weeks 3 and 4, together with accumulation of surfactant and erythrocytes within the alveolar spaces. This study defines for the first time the relationship between the immunological and pathological events during the evolution of EAG, and provides the basis for further work on the pathogenesis of Goodpasture's disease.     

Subcutaneous immunoglobulin (16 or 20%) therapy in obese patients with primary immunodeficiency: a retrospective analysis of administration by infusion pump or subcutaneous rapid push

A retrospective chart review was conducted at a single centre, capturing data on 173 primary immunodeficiency disease (PIDD) patients, including 40 obese patients, using subcutaneous administration of immunoglobulin (Ig) (SCIG) (16 or 20%) delivered by infusion pump or subcutaneous (s.c.) rapid push. Patients previously using Ig administered as intravenous (i.v.) infusions (IVIG) were converted to SCIG dosing on a 1:1 basis. In both obese and non‐obese patients, mean serum Ig levels were higher during SCIG administration (steady state) compared with IVIG administration (trough values). Similar SCIG dose : serum IgG level relationships were observed between obese and non‐obese patients, suggesting the consistent bioavailability of SCIG regardless of body mass index (BMI). The mean SCIG volume per dosing site and the mean number of dosing days per week were greater with s.c. rapid push compared with infusion pump in this cohort, but the mean number of sites per infusion session was lower with s.c. rapid push. Both methods were well tolerated. The use of 20 versus 16% SCIG in obese patients improved dosing efficiency, resulting in smaller weekly volumes (54·7 versus 74·5 ml/week) and dosing on fewer days per week (2·3 versus 3·4 days). These data do not suggest a need for SCIG dosing adjustments in obese individuals relative to non‐obese patients. The administration of SCIG using either infusion pump or s.c. rapid push is a practical and well‐tolerated alternative to IVIG in obese patients. Offering various administration techniques provides a greater opportunity for treatment satisfaction and patient empowerment, which may support high levels of patient compliance.     

冠心病患者血小板膜糖蛋白CD63;CD62P和TSD的表达

目的研究冠心病患者血小板膜糖蛋白的表达。方法采用流式细胞术(FCM) ,对113例冠心病患者及37例健康人血小板膜糖蛋白(MGP)CD63 ,CD62P和凝血酶敏感蛋白(TSD)进行了检测。结果患者组CD63,CD62P和TDS3种MGP的阳性表达率分别为 :(5.3±4.0) % ,(5.8±3.3)%和(4.7±3.7)% ,均显著高于正常对照组 ,分别为 :(1.0±0.6) % ,(1.4±0.5)%和(1.6±0.6)%(P<0.01)。结论用FCM检测活化血小板 ,结果准确 ,特异性和灵敏度高 ,可反映单个或亚群血小板质膜上活化抗原的变化 ,对血栓性疾病的诊断及治疗具有重要的意义。     

Comparison of rheumatoid factors of rheumatoid arthritis patients,of individuals with mycobacterial infections and of normal controls: evidence for maturation in the absence of an autoimmune response

We analyzed the rheumatoid factors (RF) produced by Epstein-Barr virus-transformed monoclonal B cells established from four patients with rheumatoid arthritis (RA), three individuals with a history of Mycobacterium tuberculosis (TB) and four normal controls (NI). Fifty-eight RF were analyzed for specific activity (international units-RF/μg) for the Fc part of IgG and their interaction with tetanus toxoid (TT) and DNA (polyspecificity). Furthermore, we sequenced the V-D-J heavy chain region of 16 (9TB-/7RA-) RF. Significant differences were observed between the NI-RF and the TB- and RA-RF. While the RF repertoire of normal individuals comprised of low-avidity RF of which the majority (15/17) were polyspecific, more than half of the TB- and RA-RF were monoreactive. Furthermore, the monospecific TB- and RA-RF were of significantly higher avidity than the NI-RF (RA > TB ≫ NI). With respect to poly-specificity, the RF in the three groups were comparable: the interaction with DNA, TT as well as with Fc was inhibited either by an increase of the ionic strength to 0.3–0.5 M NaCl or by addition of the polyanion dextran sulfate, indicating that the antibodies interacted with similar anionic epitopes shared by the three antigens. Analysis of the V-D-J heavy chain regions showed significant differences between the respective RF. The salt-sensitive binding was highly correlated with the presence of arginine in the complementarity-determining region 3 (CDR3). Furthermore, whereas the polyspecific RF consisted predominantly of germ-line encoded antibodies, the genes of the monospecific RA/TB-RF were somatically mutated (RA > TB). It is therefore likely that maturation of RF can be initiated by chronic infections and that monospecific, somatically mutated RF are not a unique characteristic of autoimmune diseases.     

Diagnostic features of pemphigus vulgaris in patients with pemphigus foliaceus: detection of both autoantibodies, long-term follow-up and treatment responses

There are several studies that describe the simultaneous presence and conversion of pemphigus foliaceus into pemphigus vulgaris and vice versa. We describe eight patients with clinical, histological and immunopathological features of pemphigus foliaceus, at the time of the initial diagnosis. After a mean period of 2.5 years, additional serological features of pemphigus vulgaris were observed. During a long-term follow-up, systemic therapies, their durations and treatment outcomes were recorded. These patients did not respond to conventional systemic therapy and developed multiple side-effects from these drugs. Hence, they were treated with intravenous immunoglobulin therapy (IVIg). Prior to the initiation of IVIg therapy, different assays were performed to detect the presence of autoantibodies, including indirect immunofluorescence (IIF), immunoblot assay using bovine gingival lysate, and ELISA. Twenty-five healthy normal individuals, 12 patients with pemphigus vulgaris, and eight patients with pemphigus foliaceus served as controls for comparison of serological studies. At the time of initial diagnosis, the sera of all eight study patients also demonstrated binding on an immunoblot assay to a 160-kDa protein (desmoglein 1) only. This is typically observed in pemphigus foliaceus. Prior to staring IVIg therapy, binding was observed to both the 160 kDa and 130 kDa (desmoglein 3) proteins on an immunoblot assay which was characteristic of pemphigus vulgaris. The antidesmogleins, 1 and 3 autoantibodies, were predominantly of the IgG4 subclass in all eight patients studied. IVIg therapy induced remission in four patients and control in four of the eight patients. The total follow-up period ranged from 2.6 to 9.5 years (mean 5.3 years). It is difficult to determine the exact time at which these patients with pemphigus foliaceus developed pemphigus vulgaris. It is possible that the disease was nonresponsive to conventional immunosuppressive therapy owing to the simultaneous presence of two autoantibodies.