Pathological Study on the Relationship among C4d, Complement Regulatory Factor CD59 and C5b-9 in Acute Rejection Cases

 

Shinichi Nishi1), Naofumi Imai2), Yosuke Ito2), Mitsuhiro Ueno2), Sachiko Fukase2), Yoko Takahashi2), Masaaki Arakawa2), Kazuhide Saito3), Kota Takahashi3), Gejyo Fumitake2)

Blood Purification Center, Niigata University Hospital, Niigata city, Japan 1)

Div of Clinical Nephrology and Rheumatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata city, Japan 2)

Div Urology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata city, Japan 3)

 

Background :

The deposition of C4d on peritubular capillary (PTC) is well known as a suggestive marker of humoral rejection and a poor prognostic finding.  Although the initial markers of humoral rejection, such as IgG and C3, are not confirmed on PTC, C4d is persistently remained on PTC in humoral rejection.  Additionally, whether C4d stimulates the latter complement cascade has not been clearly resolved so far.

 

Aim :

In this article, we aimed to explore the evidences of the activation of latter complement cascade in vivo study with biopsy specimens.

 

Methods and Results :

Subjective cases were 10 acute rejection (AR) patients and 10 normal controls obtained from 0 hour biopsies. Immunohistochemical method was performed by immunofluorescency. Three cases of AR group showed strong deposition of C4d on PTC and none of controls revealed it in their tissues. We evaluated the location of CD59 and C5b-9 in these cases. CD59, one of complement regulatory factors working at a latter phase of C4d deposition, was expressed on PTC in all cases of the both groups.  The deposition of C5b-9 was not confirmed on PTC in the cases with C4d deposition as well as the ones without C4d deposition.  In normal controls the deposition of C5b-9 was also absent on PTC.  However, the deposition of C5b-9 was faintly observed on tubular basement membrane (TBM) in normal controls. Five of 10 cases in AR group showed more intensive C5b-9 deposition on TBM and 3 cases with C4d deposition on PTC were included in this group.

 

Conclusion :

From our data, we could not find the colocalization of C4d and C5b-9 (MAC) in vivo.  C5b-9 is a final substance of complement cascade. After the production of C4d, complement regulatory factor CD59 inhibits the cascade activation to form C5b-9.  CD59 on PTC may affect the dissociation between C4d and C5b-9.  Additionally, we suspect more intensive deposition of C5b-9 on TBM in AR group may suggest an independent mechanism of acute rejection.

 

Title:

Pathological Study on the Relationship among C4d, Complement Regulatory Factor CD59 and C5b-9 in Acute Rejection Cases

 

Correspondence to:

Shinichi Nishi, MD.

 

Registration No. 533084

 

 

Address:

1-754, Asahimachi-dori Niigata city, Japan   Zip-code 951-754

email: snishi@med.niigata-u.ac.jp