Pemfigusta anti-desmoglein-1 ve anti-desmoglein-3 antikor serum düzeyleri ile direkt immünfloresan incelemelerin hastalık aktivitesi ve tedavi ile ilişkisi
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Date
2009
Authors
Yılmaz, Mediha
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Publisher
Uludağ Üniversitesi
Abstract
Pemfigus deri ve mukozalarda bül oluşumuyla seyreden, otoimmün bir hastalıktır. Hücre yüzey antijenlerine karşı gelişen otoantikorlar, hücrelerin adezyon özelliklerini kaybetmelerine ve bül oluşmasına neden olurlar. Antijenlerdeki farklılıklar yanında antijenlerin vücudun farklı yerlerinde, epidermisin ayrı tabakalarındaki dağılımı hastalığın farklı iki formunun oluşmasının sebebidir. Pemfigusun iki klasik formu olan pemfigus foliaseus ve pemfigus vulgariste hedef antijenler sırasıyla desmoglein-1 (dsg-1) ve desmoglein-3 (dsg-3)'tür.Otoantikorların takibinin pemfigus hastalarının izlemi ve tedavisinin yönlendirilmesinde yol gösterici olacağı düşünülmektedir. Bu çalışmada antikorların saptanmasında kullanılan iki yöntem olan direkt immünfloresan (IF) inceleme ve ELISA (anti-dsg-1, anti-dsg-3 serum antikorlarının ölçümü) yönteminin hastalık aktivitesi ve tedaviyle ilişkisi araştırılmaktadır.Çalışmaya 23'ü pemfigus vulgaris, 2'si pemfigus foliaseus tanısı almış toplam 25 hasta alındı. Hastaların tedavi öncesi ve klinik remisyonun 3., 6. ve 12. aylarındaki anti-dsg-1 ve anti-dsg-3 serum antikor düzeyleri ELISA ile araştırıldı. Eş zamanlı olarak aktif hastalıkta lezyon kenarından, remisyonda ise sağlam deri/mukozadan direkt IF inceleme yapıldı. Nüks halinde tetkikler tekrarlandı.Pemfigus vulgaris hastalarının tedavi öncesi 17'sinde (%73.9) anti-dsg-1 antikoru, hepsinde (%100) anti-dsg-3 antikoru pozitif saptandı. İki pemfigus foliaseus olgusunda tedavi öncesi anti-dsg-1 pozitif değerlerde iken anti-dsg-3 negatif saptandı. Anti-dsg-1 antikor serum düzeyleri deri şiddet skoru ile (r:0,577; p:0,003), anti-dsg-3 antikor serum düzeyleri ise oral mukoza şiddet skoru ile korele idi ( r:0,539 ; p:0,008). Tam remisyona giren hastaların 16'sında (%84,2) tedavi öncesi direkt IF'da saptanan birikim remisyonla birlikte negatifleşti. Anti-dsg-1 ve anti-dsg-3 değerlerinde remisyona girince gözlenen azalma istatistiksel olarak anlamlı bulundu (p<0,001). Takiplerinde nüks gözlenen 9 hastanın 5'inde (%55,5) remisyonda direkt IF incelemede immün birikim negatifleşmişken nüks edince pozitifleşti. Nüks gözlenen 9 hastanın hepsinde nüks sırasında anti-dsg-1 ve/veya anti-dsg-3 serum düzeylerinde artış saptandı. Dokuz olgunun 3'ünde ise klinik remisyon halinde iken nüksten 1-4 ay öncesinde serum antikor düzeylerinde yükselme tespit edildi.Bu çalışmada serum desmoglein otoantikor değerlerinin hastalık şiddeti ve aktivitesi ile ilişkili olduğunu saptadık. Hastalık aktivitesi ile paralel seyir gösteren direkt IF incelemelere göre ELISA ile serum antikor seviyelerinin ölçülmesi hastalık takibinde daha hassas bir yöntemdir. Klinik remisyon esnasında desmoglein antikorlarının seri ölçümleri takip ve tedavi modifikasyonunda yardımcı olabilir. Bu bulguların ileri çalışmalarla desteklenmesi gerekmektedir.
Pemphigus is an autoimmune disease that results in blistering of the skin and mucous membranes. Autoantibodies directed against cell-surface antigens on keratinocytes cause loss of cellular adhesion and formation of blisters. Differences in the antigens and in the distribution of these antigens in the different regions of the body and in the seperate layers of the epidermis result in different clinical forms of the disease. In two classical forms of pemphigus; pemphigus foliaceus and pemphigus vulgaris targeted antigens are desmoglein-1 (dsg-1) and desmoglein-3 (dsg-3), respectively.Measurements of the antibodies can be a guide for the clinical follow up and modification of therapy in pemphgius. In this study the relationship between the disease activity, therapy and the two methods for the detection of the antibodies; ELISA scores and direct immunofluorescence (IF) were investigated.Twenty three pemphigus vulgaris patients and 2 pemphigus foliaceus patients were enrolled in the study. Anti-dsg-1 and anti-dsg-3 antibody serum levels were measured with ELISA before therapy and in the 3th, 6th, 12th months of clinical remission. Concurrently direct IF was performed on perilesional skin in active disease, on normal buttock skin/mucosa of the lower lip in remission. The tests were repeated if relapse has ocurred.Anti-dsg-1 was detected in 17 (%73.9) pemphigus vulgaris patients, anti-dsg-3 in 23 (%100) pemphigus vulgaris patients. In two pemphigus foliaceus patients anti-dsg-1 values were positive, while anti-dsg-3 values were negative. A statistically significant correlation was seen between anti-dsg-1 antibody serum levels and skin severity scores (r:0,577; p:0,003), as well as anti-dsg-3 antibody serum levels and oral mucosa severity scores (r:0,539 ; p:0,008). Patients in whom complete remission has been observed, 16 patients? (%84,2) direct IF results detected negative. In remission decrease in anti-dsg-1 and anti-dsg-3 values was statistically significant (p<0,001). During clinical follow up in 9 patients (%36) whom relapse has occured, 5 patients? (%55,5) direct IF results became positive with relapse. In 9 patients who relapse, anti-dsg-1 and/or anti-dsg-3 serum values were increased. Three of the 9 patients, increasion of serum antibody levels have been observed 1-4 months before the relapse.In this study we observed that serum desmoglein antibody levels correlate with disease severity and activity. Measurement of serum antibody values with ELISA is more sensitive than direct IF tests which also have a paralel course with disease activity. In clinical remission serial measurements of desmoglein antibodies can serve as an adjuvant means for clinical follow up and treatment modification. These findings must be supported with further studies.
Pemphigus is an autoimmune disease that results in blistering of the skin and mucous membranes. Autoantibodies directed against cell-surface antigens on keratinocytes cause loss of cellular adhesion and formation of blisters. Differences in the antigens and in the distribution of these antigens in the different regions of the body and in the seperate layers of the epidermis result in different clinical forms of the disease. In two classical forms of pemphigus; pemphigus foliaceus and pemphigus vulgaris targeted antigens are desmoglein-1 (dsg-1) and desmoglein-3 (dsg-3), respectively.Measurements of the antibodies can be a guide for the clinical follow up and modification of therapy in pemphgius. In this study the relationship between the disease activity, therapy and the two methods for the detection of the antibodies; ELISA scores and direct immunofluorescence (IF) were investigated.Twenty three pemphigus vulgaris patients and 2 pemphigus foliaceus patients were enrolled in the study. Anti-dsg-1 and anti-dsg-3 antibody serum levels were measured with ELISA before therapy and in the 3th, 6th, 12th months of clinical remission. Concurrently direct IF was performed on perilesional skin in active disease, on normal buttock skin/mucosa of the lower lip in remission. The tests were repeated if relapse has ocurred.Anti-dsg-1 was detected in 17 (%73.9) pemphigus vulgaris patients, anti-dsg-3 in 23 (%100) pemphigus vulgaris patients. In two pemphigus foliaceus patients anti-dsg-1 values were positive, while anti-dsg-3 values were negative. A statistically significant correlation was seen between anti-dsg-1 antibody serum levels and skin severity scores (r:0,577; p:0,003), as well as anti-dsg-3 antibody serum levels and oral mucosa severity scores (r:0,539 ; p:0,008). Patients in whom complete remission has been observed, 16 patients? (%84,2) direct IF results detected negative. In remission decrease in anti-dsg-1 and anti-dsg-3 values was statistically significant (p<0,001). During clinical follow up in 9 patients (%36) whom relapse has occured, 5 patients? (%55,5) direct IF results became positive with relapse. In 9 patients who relapse, anti-dsg-1 and/or anti-dsg-3 serum values were increased. Three of the 9 patients, increasion of serum antibody levels have been observed 1-4 months before the relapse.In this study we observed that serum desmoglein antibody levels correlate with disease severity and activity. Measurement of serum antibody values with ELISA is more sensitive than direct IF tests which also have a paralel course with disease activity. In clinical remission serial measurements of desmoglein antibodies can serve as an adjuvant means for clinical follow up and treatment modification. These findings must be supported with further studies.
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Keywords
Pemfigus vulgaris, Pemfigus foliaseus, Direkt immünfloresan, Desmoglein antikorları, Hastalık aktivitesi, Pemphigus vulgaris, Pemphigus foliaceus, Direct immunofluorescence, Desmoglein antibodies, Disease activity
Citation
Yılmaz, M. (2009). Pemfigusta anti-desmoglein-1 ve anti-desmoglein-3 antikor serum düzeyleri ile direkt immünfloresan incelemelerin hastalık aktivitesi ve tedavi ile ilişkisi. Yayınlanmamış uzmanlık tezi. Uludağ Üniversitesi Tıp Fakültesi.