THE ROLE OF MICROVASCULAR INJURY ON STEROID AND OKT3 RESPONSE IN RENAL ALLOGRAFT REJECTION  

 

Ozdemir BH, Demirhan B, Haberal M*

Departments of Pathology and General Surgery*, Başkent University Faculty of Medicine, Ankara, Turkey

 

Although it has a powerful immunosuppression activity, the use of OKT3 is associated with an increase morbidity and mortality. In order to define patient subsets must likely to benefit from OKT3 we performed a study to understand the influence of HLA-DR positive microvascular (MV) injury on the steroid and OKT3 response in acute rejection (AR).

We examined 94 biopsies of 40 renal transplant recipients. Of 40 cases 20 had showed steroid resistant AR (group 1) and received OKT3 treatment. Remaining 20 cases had showed steroid responded AR (group 2). All biopsies were immunostained with antibodies specific for HLA-DR, fibronectin (FN), CD-68, CD-3 and Factor VIII-RA. Five normal kidneys used as control. The expression of HLA-DR, FN, CD-68 and CD-3 were graded from 1 to 3.

The MV-DR expression was marked in 5 normal kidneys. The degree of MV-DR expression was decreased with increasing AR grade (p<0.01). There was a negative correlation between MV-DR expression and the degree of interstitial mononuclear cell infiltration (p<0.001). As the severity of MV destruction increases the response to steroid and OKT3 therapy declines (p<0.05). In group 2 severe MV injury was found only in 15% of cases (3/20 cases). Whereas severe MV injury was found in 55% of cases (11/20 cases) in group 1 (p<0.01). After OKT3 treatment 70 % of cases in group 1 responded to therapy. Remaining 6/20 cases (30%) that had no response to OKT3 showed severe MV injury. Only 45.5% (5/11 cases) of 11 cases with severe MV injury showed response to OKT3 therapy. The follow-up biopsies of all cases with severe MV injury showed significant interstitial fibrosis (IF) and FN expression (p<0.01). The mean time between transplantation and diffuse IF was found significantly shorter in cases with severe MV injury (p<0.01).

The destruction of DR positive microvessels would contribute to severe inflammatory reactions and subsequently to poor steroid response, early interstitial fibrosis and graft dysfunction. We concluded that the severity of MV injury predict the treatment response and graft outcome in cases with AR.

 

 

 

THE ROLE OF MICROVASCULAR INJURY ON STEROID AND OKT3 RESPONSE IN RENAL ALLOGRAFT REJECTION  

Ozdemir BH, Demirhan B, Haberal M*

Departments of Pathology and General Surgery*, Başkent University Faculty of Medicine, Ankara, Turkey

 

 

 

Correspondence address:

 

B. Handan  Ozdemir MD

Associate Professor

Department of pathology

Baskent University, Faculty of Medicine

Baglar caddesi  194-6

06700 GOP

Ankara, Turkey

Ph:   +90-312-2126591

Fax: +90-312-2127572

e-mail: handan27@hotmail.com