Complement membrane attack complexes in pathologic disc tissues.

STUDY DESIGN: 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. SUMMARY OF BACKGROUND DATA: 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.

Blood clots in vessels surrounding symptomatic nerve roots in disc herniation patients: a pilot study.

Mechanical compression and biochemical influences, e.g. by various inflammatory cells and mediators, have been suggested to be involved in the pathophysiology of sciatica. In addition, it has been suggested, but so far not clearly demonstrated, that blood pooling in the venous blood vessels surrounding nerve roots may contribute to impaired nerve root function and sciatica. There is also more direct evidence from studies on an animal model that nucleus pulposus (NP) tissue may induce blood vessel thrombosis. In the present study, a specific monoclonal antibody to platelet membrane glycoprotein complex GPIIb-IIIa was used for direct visualization of blood clots in tissue samples removed from the vicinity of symptomatic nerve roots in 20 disc herniation (DH) patients. For 12 patients, the DH was primary, for 7 patients recurrent and for 1 patient the index operation was for root canal stenosis following a DH operation 3 months earlier. Blood clots immunoreactive to GPIIb-IIIa were observed in small blood vessels in 11/20 tissue samples (55%), in 5/12 patients (42%) with primary DH and in 5/7 patients (71%) with recurrent DH. The presence or absence of GPIIb-IIIa complex immunoreactivity did not show a statistically significant relationship with pain duration, DH type (primary or recurrent), gender or straight leg raising (SLR). Thus, though immunohistochemically demonstrable, the observed periradicular blood clots could not be established to have a clinical role in sciatica in this pilot study.