Serological Studies in Bullous Pemphigoid: A Literature Review of Antibody Titers at Presentation and in Clinical Remission- Full HTML – Acta Dermato-Venereologica

Serological Studies in Bullous Pemphigoid: A Literature Review of Antibody Titers at Presentation and in Clinical Remission- Full HTML - Acta Dermato-Venereologica

AEP is commonly a diagnosis of exclusion, as diagnostic testing is nonspecific. It is a characteristic feature of many skin diseases and an unusual sign of some systemic diseases.1, 2 Pruritus may be localized or generalized and can occur as an acute or chronic condition. The aim of the present study was to determine the fine specificity of the pathogenically relevant Abs in this experimental model of BP. His doctor decided to send him home with the medication and the treatment but after two days he started to produce new shoots and in this way he has now blisters into same area where he had before. Finally I was able to lower 1mg EOD for another year till I got down to 0mg. Most often, I have to take steroids to resolve the symptoms. Positive titers were also reported in 67.6% of patients evaluated by ELISA.

In 100% of patients in whom immunoblotting was performed the titers became negative. Most of them small blisters and lesion; some healed with white mark while others on still open. The correlation between anti-basement membrane zone antibodies and the clinical course of bullous pemphigoid requires further and long-term studies. Key words: anti-basement membrane zone antibodies; remission; indirect immunofluorescence; ELISA; clinical correlation; bullous pemphigoid. I hope you can find some comfort from talking to people, telling your story & hearing theirs on this site, it’s a great forum with alot of inspiring info. One of the kids had stayed home about a month and a half ago with Impetigo. The pathogenesis of BP is characterized by tissue-bound and circulating IgG auto-antibodies against two components of the hemidesmosome of stratified epithelia, referred to as BP 230 kDa (BPAg1) and BP 180 kDa (BPAg2) (5, 6).

That’s what led me to post this. BPAg2 is a transmembrane adhesion molecule with several collagenous extracellular domains (7). In the neonatal mouse model, antibodies to BPAg2 appear to be important in subepidermal blister formation in mice (8, 9). My disease has not spread to other mucous sites. Schmidt et al. (12) first demonstrated a positive correlation between clinical disease activity and antibodies to BPAg2 as detected by enzyme-linked immunosorbent assay (ELISA). This correlation was similar to that observed between the auto-antibodies to desmogleins in patients with pemphigus vulgaris (13).

However, the positive correlation in BP was contrary to earlier observations using the standard indirect immunofluorescence (IIF) assay (14–18). Hence, the role of the antibodies to both BPAg1 and BPAg2 during the clinical course of the disease is not fully understood. I found a disease called behcets which mildly resembled my symptoms so I went to see an immunologist privately hours away who specialised in it. Herpes Simplex infection can be transmitted during pregnancy and delivery. The specific dermatoses of pregnancy. Incomplete phenotypes, disease associations and particular pathological constellations may occasionally however make diagnosis a challenging task. When evaluating the patient’s serum zinc level, blood must be collected in plastic or acid-washed tubes since regular glass tubes may be contaminated with zinc.

About 14% of kids with eczema had toothaches, compared with 10% of kids without eczema. Moreover, many of these studies had few patients or case reports, and lacked information on antibody titers during the course of the disease. More importantly several studies not included in this review lacked data on treatment and follow-up of patients after treatment was begun. View Feedback It is recommended that osteoporosis prevention should be instituted at the outset of long-term steroid therapy. When the diagnosis is not apparent, laboratory studies may be indicated. He differentiated a papular dermatitis from prurigo gestationis, which is clinically similar, on the grounds of biochemical alterations (raised levels of β-HCG in urine, lowered plasma cortisol levels) and reported a dramatically increased fetal death rate (early miscarriage and miscarriage in previous pregnancies were included!)11. The following information was obtained from each study: number of patients treated, patients’ demographics, initial systemic treatment, and treatment at the end of the period when available, serological studies that included auto-antibody titer before and at the end of the study period.

The serological values were determined by IIF, using monkey esophagus (ME) or normal human skin (NHS) as a substrate, with a standard or SSS technique, and by ELISA and immunoblotting (IB). Here we describe the characterization of a novel interacting partner of the septin family, initially cloned from a human testis expression library following yeast two-hybrid isolation to identify SEPT9 binding partners. Multinomial logistic regression revealed increased probability of Marsh 3a or greater changes with increasing TTGA or EMA levels. Serological remission is defined as the total absence of antibodies against the BMZ in the sera of the patient. The data from nine reports, which included 143 patients, is presented in Table I. 1995;14:290-296. Specific data about the number of patients on different systemic and/or topical treatments was not available for two reports (17, 24).

All patients clinically improved with the treatment(s) they received (12, 16, 17, 19–24). However, eight patients still had mild disease at the end of the study period (5.59%) (12, 20, 22). Seventy-eight (54.5%) of these patients were still receiving systemic therapy, and in 53 (37%) systemic therapy was discontinued at the time of reporting. In 10 patients (6.9%) the authors indicated that the patients were in clinical remission, but did not specify whether these patients were still receiving therapy (19). Twenty patients (13.9 %) developed a recurrence after they stopped systemic therapy or were on minimal maintenance therapy without disease (12, 16, 19, 20, 24). Four patients (2.7%) deliberately stopped their medications (12, 24). Two patients (1.39%) treated with only prednisolone died of a massive gastrointestinal bleeding and a Gram-negative septicemia (16).

CR: complete remission; NA: not available; Ca: Caucasian; A: Azsiatic; AA: African Americans; ID: index value = (patient serum OD – negative control OD)/(positive control OD – negative control OD) × 100; OD492: optical density; tap: tapered; unch: unchanged; IVIg: intravenous immunoglobuline; C: corticosteroids; AZA: azathioprine; T: tetracycline; N: nicotinamide; D: dapsone; CY: cyclophosphamide; Cycl: cyclosporine; PL: plasmapheresis; TS: topical steroids; PM: pulse with methylprednisolone. Serological analysis using IIF prior to, and at the end of, the study period was performed on 118 patients (82.5%). In 62 patients (52.5%) ME, and in 56 patients (47.4%) NHS was used as substrate. Of these 56 patients, in 42 (75%) SSS IIF studies were performed. Among the 62 patients whose sera was evaluated by IIF using ME, 51 (82.2%) were positive prior to therapy. In 18 patients (29%) the antibody titers remained positive at the end of the study period (16, 17). Among the 56 patients whose sera was evaluated by IIF using NHS, 55 (98.2%) were positive prior to therapy.

At the end of the study period, 45 (80.3%) continued to remain positive (12, 20, 23, 24), of which in three patients (6.6%) the anti-BMZ antibody titers were increased (20, 23). Antibodies against BPAg2 were studied in only 71 of the 143 patients (49.6%), using ELISA (rNC16a domain). Among these, in 65 (91.5%) the ELISA levels were positive prior to beginning systemic therapy (12, 19, 20, 22–24). In 48 patients (67.6%) at the end of the study period (12, 19, 20, 22–24) the ELISA was still positive, of which 40 patients (83.4%) were in complete clinical remission and eight patients (16.7%) still had mild disease. The levels of the antibodies to BPAg2 were lower when compared with pre-treatment levels. Among these 48 patients, only one (2.08%) showed an increased mean index value (20). In 23 patients (32.2%) at the end of the study period when no clinical disease was present no antibodies were detected (12, 19, 20, 22–24).

Antepartum surveillance is recommended for patients with intrahepatic cholestasis of pregnancy, impetigo herpetiformis, and pemphigoid gestationis. Roger D, Vaillant L, Fignon A, Pierre F, Bacq Y, Brechot JF, et al. While different substrates were used for the detection of pemphigus autoantibodies, monkey esophagus has gained a wide acceptance as a sensitive substrate. Among 136 babies who used a pacifier during their first 6 months of life, 65 had parents who reported sucking on the pacifiers to clean them. Lio said. The comparison of serological data using IIF and ELISA on the patients prior to therapy and the end of the study period is presented in Fig. 1.

In some patients only IIF was performed, in others only ELISA, and in some both IIF and ELISA. 2007, 87: 291-294. Fetal prognosis is generally good but there is an increase in prematurity and small-for-date babies. Statistical analysis was not possible in comparing the antibody levels in the various groups because of differences in the assay techniques and the methodologies used in different studies. However, it is clear that after treatment in the majority of patients there is a reduction in the antibody titer by IIF and BPAg2 ELISA, and by IB testing. We propose that, during mitosis, robust sister chromatid cohesion along chromosome arms requires both condensinand cohesin-dependent mechanisms, which function independently of each other. In 1968, the term hypereosinophilic syndromes (HES) was coined to refer to a spectrum of eosinophil-associated diseases presumed to be caused by an underlying immunological pathology.

Serological Studies in Bullous Pemphigoid: A Literature Review of Antibody Titers at Presentation and in Clinical Remission- Full HTML - Acta Dermato-Venereologica
Fig. 1. Zirwas MJ, Seraly MP. In some patients only IIF was carried out, in others only ELISA, and in some both IIF and ELISA. The titers of anti-basement membrane zone (anti-BMZ) antibodies are presented in the total number of patients studied, levels prior to treatment and at the end of the study period. In a sinificant majority of the patients there is a reduction in the antibody titer after treatment as detected by IIF, ELISA, and IB. Data compiled from refs 12, 16, 17, 19–24.

In 56 patients (39.1%) sera were evaluated using both IIF and ELISA BPAg2 (12, 20, 23, 24). The comparison of these data is presented in Fig. 2. In these patients the anti-BMZ antibody titers by IIF using NHS is compared with BPAg2 ELISA values. These data are compared in the total number of patients pre-treatment and at the end of the study period, indicating an increase or decrease in the antibody titer. Fig. 2.

Sera were evaluated in 56 patients using both indirect immunofluorescence (IIF) and enzyme-linked immunosorbent assay (ELISA) BPAg2. In these patients the anti-basement membrane zone (anti-BMZ) antibody titers by IIF using human skin (HS) are compared with BPAg2 ELISA values. These data are compared for the total number of patients pre-treatment and at the end of the study period (12, 20, 23, 24). Information on the initial treatment divided into treatment groups was available for only six studies (12, 16, 19, 20, 22, 23), which included 80 patients (55.9%). The numbers of patients in each category were as follows: 41 patients were treated with corticosteroids (51.25%) only, 27 patients with corticosteroids and immunosuppressive agents (33.75%), 12 patients with anti-inflammatory agents (15%), 7 patients with topical steroids only (8.75%). The results for the serological studies were recorded for each study simultaneously. In three studies (17, 21, 24) such information could not be obtained from the data provided.

In one study all patients received corticosteroids and the number that received immunosuppressive drugs was not clear (24). In the second study data was available only on IB but not on IIF or ELISA (21). In the third there was a lack of description of subgroups of patients in whom serological studies were performed (17). This analytical review presents data on 143 patients with BP who fulfilled the inclusion criteria. These patients were treated with a large spectrum of systemic agents. 18. Occasionally, genital, nasal and ocular mucosal surfaces are also affected [51-54].

Miami Beach, Fla.— The field of alternative medicine is increasing in popularity among dermatologists in the United States, particularly among their patients. What better person to design a plan that takes into account the special sensitivities of patients than the primary care clinician working in the medical home model? When IIF is performed prior to initiating systemic therapy, using ME and NHS (standard or salt-split), 82.2% and 98.2% of patients, respectively, are positive. ELISA for BPAg2 is positive in 91.5% of patients and the IB assay identified antibodies to BPAg2 in 90% of the patients tested and to BPAg1 in all the patients. Therefore, it appears that when DIF is positive there is statistically no significant difference in the likelihood of detecting anti-BMZ antibodies using IIF, ELISA or IB. Until 2004, discussion on the comparison of the sensitivity between ELISA and IIF for measuring antibodies in BP sera was confusing because different technologies were employed (25, 26). The reason for this defect seems to be multifactorial with genetic, hormonal, and exogenous factors being involved25.

While no International Consensus Development conference has been organized to debate and define this issue, reading the literature there appears to be an informal agreement between authors that ELISA has greater sensitivity for antibodies in BP, compared with IIF (29, 30). Analysis of the data highlight several important observations that have clinical relevance and consequence. The article explores the reasons why Virginia chose to establish its public health institute outside government and demonstrates how development of the institute is changing community health improvement in the state. PURPOSE: A retrospective study was conducted at three centers to examine the participation of neutrophils and eosinophils in the inflammatory processes associated with atopic keratoconjunctivitis (AKC) and vernal keratoconjunctivitis (VKC). (iii) Using the BPAg2 ELISA, 67.6% of patients tested had positive levels, though the levels were decreased; among these patients only eight had still mild disease at the end of the study period. In one patient (2.1%) an increase in the ELISA value was observed and this patient had mild disease at the end of the study period (20). These data collectively suggest that in the group of patients with BP studied, it appears that a serological remission does not accompany a clinical remission.

In the small number of patients preliminary observations would suggest that amongst the assays used to determine the anti-BMZ antibody titers at the beginning of the therapy, and at the end of the study period, it would appear that the best correlation, if any, is observed in IIF with ME. Hence, there is a significant value in doing serological studies in BP patients prior to therapy. The value and benefits of such study during the clinical course or at the time of clinical remission might require further studies and follow-up. The authors of the present paper realized that the substrates used in the IIF might influence results. This is particularly true for ME and NHS. However, the ELISA is based on the NC16a extracellular domain of BP180, and several authors have demonstrated its value in the BP (19, 22, 31, 32). Other investigators suggest that additional epitopes in the intracellular and extracellular portion of BP180 might be useful if included in the ELISA (33, 34).

Interestingly, in a small number of patients who developed recurrence of the disease, a rise in the levels of BPAg2 detected in the ELISA were observed, demonstrating that this might be of some predictive value in clinical management (12, 16, 19, 20, 24). The presence of anti-BMZ antibodies in the absence of clinical disease opens an avenue for research into the role of these antibodies in the pathogenesis of the disease. While there is minimal data to provide any explanation, three possibilities exist. The first is the phenomenon of “epitope spreading” (34). Secondly, the subclass of the IgG and a switch between the subclasses may play a role (35–37). Thirdly, long-lived plasma cells may produce non-pathogenic antibodies (38). Such cells have immunological memory and may be sequestered in the bone marrow or spleen (39), where they may survive for long periods.

Such cells are frequently resistant to conventional immunosuppressive therapy (40, 41) and rituximab (42). An additional four different studies have demonstrated that serum levels of anti-BPAg2 antibodies detected by ELISA appear to parallel the disease activity (43–46). This trend was demonstrated in all IgG subclasses (45). However, these studies were not included in our analysis because they did not fulfill the inclusion criteria. The levels of presumed pathogenic autoantibody do not necessarily reduce or disappear in several autoantibody-mediated diseases. In some recent studies in certain disease, such as proteinase-3-associated vasculitis (47), Graves’ disease (48) and multiple sclerosis (49), there appears to be a good correlation between clinical remission and marked reduction or absence of detection of pathogenic autoantibody. However, in other diseases, such rheumatoid arthritis and systemic lupus erythematosus, such distinct correlations are not always present (50, 51).

The effect of therapy on antibodies was described clearly in only one study (12). In this study antibody titers decreased in patients on corticosteroids, while those on other anti-inflammatory drugs showed minimal or no change. This would indicate that initial and subsequent therapy could affect antibody status at the end of the therapy. Since indirect IF microscopy has a sensitivity of about only 50% in IgA pemphigus, a more sensitive IF molecular assay has been developed using desmocollin-transfected COS-7 cells [65]. The “riskiness” of a given medicine is usually very closely associated with its potency and therapeutic effect, and according to Dr. Researchers worked to determine whether patients stayed symptom-free for six months at six-month intervals. Nonetheless, it appears that there is a trend to suggest that the incidence of lower titer of antibodies was observed in patients treated with corticosteroids and/or immunosuppressive agents compared with these on other anti-inflammatory agents.

In the opinion of the authors the analysis of the data provides some relevant and important clinical insights into the management of BP. However, there are some limitations that need to be addressed. First, the procedures for IIF are not standardized or uniform. Of these, two-thirds present with widespread eczematous changes (so-called E-type AEP) often affecting typical atopic sites such as face, neck, décolleté, and the flexural surfaces of the extremities, while one-third have papular lesions (P-type AEP)3. The third limitation is the lack of uniform data on disease severity. Fourthly, there is a lack of long-term follow-up in the majority of studies. Fifthly, there is a lack of standardized statistical analysis.

CONCLUSION: In patients with BP, who are nonresponsive to conventional therapy, the presence of two autoimmune diseases or a dual diagnosis should be considered. Performing statistical analysis on the 143 patients in this review would be inaccurate. Therefore we have refrained from statistical comparisons of the data in this paper. In conclusion, the questions addressed by us can be answered as follows: (i) there is a high incidence of the presence of anti-BMZ antibodies in patients with BP prior to the initiation of therapy. When the patients are in apparent clinical remission 30–50% have the presence of detectable levels of anti-BMZ antibodies, although the titers are decreased. (ii) The data provided by the investigators individually and collectively do not permit meaningful analysis of the correlation between the disease severity and the levels of anti-BMZ antibodies. (iii) In a limited and preliminary manner, it appears that immunosuppressive therapy reduces the auto-antibody titers more effectively than does pure anti-inflammatory therapy alone.

The authors are grateful to Olga Lyczmanenko, BA, MA, MLIS, library manager and Christopher Vaillancourt, BA, MA, MLIS of the Woodard Library of the New England Baptist Hospital for their assistance in the preparation of this paper.

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