Complement membrane attack complexes in pathologic disc tissues.
METHODS
Complement membrane attack complexes were located in lumbar spine disc tissues by immunohistochemistry. Their occurrence was compared in control discs obtained from organ donors (CD), discs showing a normal macroscopic anatomy, samples of intervertebral disc herniations (DH), and intervertebral discs found to be degenerated by discography, but not herniated (DD).


OBJECTIVE
To look for a possible role of complement activation, specifically complement membrane attack complexes, an end product of the classic immune complex-mediated complement activation pathway, in disc pathophysiology.


BACKGROUND
Recent immunohistochemical and biochemical studies suggest a possible role for immune complexes, as observed by immunohistochemical location and biochemical assay of immunoglobulins M and G in intervertebral disc pathophysiology. Immune complexes may trigger complement activation and ultimately cell lysis. There are, however, currently no reports on complement activation in disc tissues, although immune (antigen-antibody) complexes have been demonstrated. Such immune complexes have been reported to occur on or near to disc cells in DH tissues.


METHODS
Thin frozen sections of disc tissue from CD (n = 9 discs), DH (n = 58 discs), and DD (n = 11 discs) were cut and then immunostained with a monoclonal antibody to the complement membrane attack complex (C5b-9) using avidin-biotin complex (ABC) immunostaining. The presence or absence of complement membrane attack complex immunoreactivity was compared in the various subtypes of DH and also with preoperative duration of radicular pain.


RESULTS
Complement membrane attack complexes could be observed in none of the CDs studied. In contrast, in more than one third of both the DH (21/58, 36.2%) and the DD (4/11, 36.4%), immunoreactivity to complement membrane attack complexes could be observed in disc cells. In DD discs, immunoreactivity to complement membrane attack complexes was most often present in anulus fibrosus samples (5/13, 38.5%). With respect to subtype of DH, complement membrane attack complexes were observed in 19 of 36 sequestrated discs (52.8%), 1 of 16 extrusions (6.3%), and 1 of 6 protrusions (16.7%). Complement membrane attack complexes were more often present with shorter pain duration (P= 0.03), but showed no relation to age. Disc cells often showed a heavy staining pattern for complement membrane attack complexes, suggesting an abundance of these complexes lodged in the membrane of the cells.


CONCLUSIONS
The predominant presence of complement membrane attack complexes in sequestrated disc tissue could suggest a role in DH tissue-induced sciatica. Possibly immune (antigen-antibody) complexes, reported in previous studies, trigger the classic pathway of complement activation, with complement membrane attack complexes as the final product. Complement membrane attack complexes also appear to have some as yet undefined role in degenerated nonherniated disc tissue, with a predominant presence in the anulus fibrosus cells of such discs.
Grönblad
Mats
M
Spine Research Unit Research Laboratory, Department of Orthopaedics and Traumatology, Institute of Surgery, University Central Hospital, University of Helsinki, Finland. mats.gronblad@hus.fi
Habtemariam
Aklilu
A
Virri
Johanna
J
Seitsalo
Seppo
S
Vanharanta
Heikki
H
Guyer
Richard D
RD
D000328:Adult; D000368:Aged; D015938:Complement Membrane Attack Complex / Q000032:analysis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007403:Intervertebral Disc / Q000737:chemistry* / Q000473:pathology*; D007405:Intervertebral Disc Displacement / Q000473:pathology*; D008161:Lumbosacral Region; D008297:Male; D008875:Middle Aged
D015938:Complement Membrane Attack Complex