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Biomedical subjects

W C Watson

Publications and source records attributed to W C Watson.

At least 19 recordsLinked to original sources
PubMed1999

Outcome of moderate carotid artery stenosis in patients who are asymptomatic.

PURPOSE: The incidence rate of disease progression and stroke after the diagnosis of a moderate (50% to 79%) carotid stenosis was determined by means of color-flow duplex scanning. METHODS: During a 4-year period, 344 male veterans with moderate internal carotid artery stenoses, on one or both sides, were examined at regular intervals for a mean period of 25 months. Carotid color-flow scans were obtained semiannually. Clinical follow-up was performed to determine the incidence rate of amaurosis fugax, transient ischemic attacks, nonhemispheric symptoms, and strokes. RESULTS: New neurologic symptoms developed in 75 patients (21.8%). Fifty-one (14.8%) had ipsilateral symptoms during follow-up: 18 amaurosis fugax (5.2%), 14 transient ischemic attacks (4%), 5 nonhemispheric symptoms (1.4%), and 14 strokes (4%). Twenty-four patients (6.9%) had contralateral symptoms: 20 strokes (5.8%) and 4 transient ischemic attacks (1.2%). Life-table analysis showed that the annual rate of ipsilateral neurologic events was 8.1%, and the annual rate of stroke was 2.1%. Seventy-five patients (22%) died in the follow-up period. Disease progression to 80% to 99% stenosis or occlusion occurred in 71 of 458 vessels (15.5%). The internal carotid arteries that showed evidence of disease progression had a significantly higher initial peak systolic velocity (251 vs 190 cm/s; P <.0001) and end diastolic velocity (74 vs 52 cm/s; P < 0.0001). Black patients and patients with ischemic heart disease were at a higher risk for disease progression. We could not identify any atherosclerotic risk factors that reliably predicted patients in whom future ipsilateral neurologic symptoms were more likely to develop. However, there was an increased risk of stroke associated with progression of disease. CONCLUSION: Patients who are asymptomatic and who have moderate carotid stenoses are at significant risk for neurologic symptoms and death, but have a relatively low incidence rate of ipsilateral events. The initial flow characteristics in the stenotic vessel are predictive of future disease progression, but they are not helpful in identifying patients in whom symptoms will develop.

Adult↗
PubMed1998

The Xylum Clot Signature Analyzer: a dynamic flow system that simulates vascular injury.

The Xylum Clot Signature Analyzer (CSA) is an automated, user-friendly, benchtop analyzer that assesses platelet function and coagulation in non-anticoagulated whole blood under physiological flow and temperature conditions. From blood drawn in a single venipuncture, the CSA measures: a) the time for platelets to occlude holes "punched" in a blood conduit (platelet hemostasis time or PHT); b) collagen-induced thrombus formation (CITF) as blood flows in a channel containing a collagen fiber; and c) clotting time (CT). Micrographs show platelet-rich thrombi in the punched holes and on the collagen surface after a run. PHT and CITF increased at lower shear rate, suggesting that shear activation of platelets is involved in hole closure and in collagen-induced thrombus formation. In blood mixed with anti-von Willebrand's factor (vWF) antibodies, anti-GPIb antibodies, aurin tricarboxylic acid (ATA), or anti-GPIIb-IIIa, PHT and CITF were prolonged, further supporting the reflection of platelet function by those parameters. At low shear rate (<1000 sec(-1)), native blood and blood treated with anti-vWF did not have significantly different PHTs or CITFs. At high shear rate (>6000 sec(-1)), the PHT and CITF of the anti-vWF-treated sample were significantly greater than those of the untreated sample. This supports the inhibition of shear-induced activation of platelets by anti-vWF in the CSA. Heparin-treated blood showed significantly longer CT, indicating that coagulation of blood under flow is inhibited by heparin. The CSA thus assess multiple aspects of hemostasis under near-physiological conditions.

Biological Assay↗
PubMed1998

Acute effects of intermittent pneumatic compression on popliteal artery blood flow.

OBJECTIVES: To investigate the immediate effects of intermittent pneumatic foot and calf compression (IPFCC) on popliteal artery blood flow in symptom-free volunteers and to determine the reproducibility of color flow duplex imaging in the popliteal artery. DESIGN: Cohort study. SETTING: A university associated tertiary care hospital. PATIENTS: Forty lower limbs of 30 volunteers without symptoms or noteworthy risk factors of peripheral vascular disease. INTERVENTIONS: Popliteal artery blood flow was measured in the sitting position before, during, and after the application of IPFCC using color flow duplex imaging. The interobserver, intraobserver, and between occasion within-subject variability of the popliteal artery blood flow were evaluated in 5 symptom-free volunteers who had at least 5 color flow duplex imaging measurements taken at each of the above time points on 3 different days. MAIN OUTCOME MEASURES: The arterial diameter, peak systolic, end diastolic, and reverse-flow velocities were measured, as well as the duration of forward flow during diastole before, during, and after IPFCC. The same variables were measured in 5 separate volunteers by 3 different observers, on 3 separate days, at 3 separate times to determine reproducibility. RESULTS: Including all types of variability, the popliteal artery blood flow varied from 8% to 39% with a mean value of 19%. Since the diameter of the artery was obtained with less than 5% variability, the time average mean velocity was responsible for the high variation in flow. During application of the IPFCC, the popliteal artery blood flow increased significantly in all subjects (P<.001). The mean increase in the flow was 2.4 times the baseline values. The diameter of the arteries remained unchanged while the time average velocity increased significantly (P<.001). This velocity increase was due to marked elevation in the peak systolic and end diastolic velocities and diminution of the reverse-flow component, as well as a prolongation of the forward flow during diastole. After cessation of the pump, flow returned to baseline levels (P=.41) CONCLUSIONS: Ultrasound-derived popliteal artery blood flow measurements show moderate variability. The application of IPFCC greatly enhances popliteal artery blood flow. The flow increase is due to a dramatic drop in the peripheral vascular resistance as the peak systolic and end diastolic flow velocities increase and the reverse-flow component diminishes. Its role in the treatment of lower extremity occlusive arterial disease needs to be determined.

Adult↗
PubMed1998

Intra-aortic balloon counterpulsation in patients with severe cardiac dysfunction undergoing abdominal operations.

OBJECTIVE: To assess the effectiveness of intra-aortic balloon counterpulsation (IABC) as adjunctive treatment in patients undergoing abdominal operations. DESIGN: Retrospective review of patient medical records to determine the incidence of mortality following abdominal surgery and the incidence of complications from IABC. SETTING: University-based, tertiary care hospital. PATIENTS: Sixty-eight patients who underwent an abdominal operation and IABC during the same hospitalization were divided into the following groups: Group 1, IABC initiated prior to operation to enhance perioperative cardiac function; group 2, IABC used to treat cardiogenic shock in a patient who subsequently required an operation while undergoing IABC; and group 3, IABC device inserted and removed for treatment of cardiogenic shock in a patient who subsequently required an operation within 30 days of removal of the device. MAIN OUTCOME MEASURES: The incidence of mortality in IABC-supported patients and IABC-related complications. RESULTS: In group 1, excluding 3 patients who died following emergency operation, 26 patients underwent nonemergency procedures and had a 12% mortality rate. In group 2, 5 of 6 patients who underwent emergency operations died, whereas 3 of 4 patients who required only urgent operations survived. In group 3, 18 (62%) of 29 patients who underwent urgent or emergent operations died postoperatively. Thirteen patients experienced complications related to IABC; there were no deaths and no limbs were lost to ischemia. CONCLUSIONS: This is the largest reported series looking at the utility of IABC as adjunctive treatment for patients undergoing abdominal operations. The outcome for those patients requiring emergency operations remains poor, but it is likely that more liberal use of IABC in patients with severe cardiac dysfunction who require nonemergency operations may improve patient outcome.

Abdomen↗
PubMed1998

Immunity to type IX collagen in rodents: a study of type IX collagen for autoimmune and arthritogenic activities.

Type IX collagen (CIX), a cartilage-specific glycoprotein, constitutes < or = 10% of cartilage collagen. To ascertain whether CIX can induce arthritis as shown for type II and XI collagen (CII and CXI), outbred rats were sensitized with bovine, chick and human CIX; inbred rats, mice, and guinea pigs were sensitized with bovine CIX. Mice and guinea pigs proved resistant to arthritis, as did rats sensitized with CIX/Freund's incomplete adjuvant (FIA). Arthritis was seen in rats when 100 microg of Mycobacterium tuberculosis (Mtb) were added to FIA, but seldom with smaller doses of Mtb, suggesting the arthritis was adjuvant-induced. High levels of antibodies to rat CIX, containing complement-fixing subclasses, were detected in rat sera in addition to DTH and lymphocyte proliferation responses to rat CIX. Given the potential for CIX-induced disease, CIX-sensitized rats were injected intraperitoneally with lipopolysaccharide (LPS) to stimulate proinflammatory cytokine release, and intra-articularly with rat CIX to stimulate arthritis. LPS stimulation was ineffective; however, intra-articularly injected CIX produced transient synovitis. When rats with stable adjuvant arthritis were sensitized with CIX/FIA, significant increases in paw volume were measured compared with controls given CI/FIA. Immunohistochemical studies of actively and passively sensitized rats revealed deposits of CIX antibody, but not C3, at the joint margins where proteoglycan staining was weak. Together, these findings suggest that autoimmunity to CIX, in contrast to CII and CXI, is not directly pathogenic but may contribute to joint injury provided arthritis is initiated by an independent disease process.

Animals↗
PubMed1997

Carotid endarterectomy for recurrent stenosis.

PURPOSE: The purpose of this study was to report our results in the surgical management of recurrent carotid stenosis (RCS) after carotid endarterectomy (CEA). METHODS: In a 20-year period, we performed 1209 CEAs; 82 operations (6.8%) were for RCS. There were 33 men and 36 women, with an average age of 66.3 years. Nine patients underwent two redo CEAs and two patients underwent three redo CEAs for either bilateral recurrence or a second recurrence on the same side. Overall, 10 patients were identified with a second recurrence. RESULTS: The average time to presentation with RCS was 65 months (range, 3 to 361 months). The majority of patients (66%) were symptomatic, 34% had transient ischemic attacks, 17% had amaurosis fugax, 9% had strokes, and 6% had nonhemispheric symptoms. Before repair, angiograms were obtained. Patch repair was performed in 61 procedures (74%), 41 with vein, 11 with Dacron, and nine with polytetrafluoroethylene. Autogenous or synthetic bypass grafts were used in 20 procedures (24%), vein in eight, Dacron in two, and polytetrafluoroethylene in 10. In one patient, an occluded internal carotid artery was ligated and an endarterectomy of the external carotid artery was performed without a patch. The operative stroke rate was 4.8%. Minor complications included transient or permanent cranial nerve deficits in 7.3% and wound hematomas in 2.4%. CONCLUSION: Although repeat endarterectomy to treat RCS is technically more demanding, it can be performed safely. Long-term follow-up examination shows that a second recurrence may develop, and we recommend serial noninvasive testing.

Aged↗
PubMed1996

Autoantibodies to murine type II collagen in collagen-induced arthritis: a comparison of susceptible and nonsusceptible strains.

Collagen-induced arthritis (CIA) is an experimental autoimmune disease elicited in genetically susceptible strains of mice by immunization with heterologous type II collagen. This experimental disease is mediated by the immune response of both T cells and B cells, and susceptibility is restricted by the class II molecules of the MHC. In this study we identify specific epitopes bound by autoantibodies elicited through immunization of several haplotypes of C57BL/10 mice with chick alpha1 (II)-CB11. ELISA analysis using a panel of 15-mer murine type II collagen peptides revealed a pattern of autoantibody epitope specificity that was remarkably similar among CIA-susceptible and nonsusceptible congenic strains, regardless of class II haplotype. However, one epitope was identified that was bound only by autoantibodies from CIA-susceptible strains bearing I-A(q) (B10.Q and B10.QbetaBR). In addition, this epitope was also present within affinity-purified Ab obtained from the CIA-susceptible strain DBA/1 (I-A(q)). Analyses of immune serum from B10.Q and B10.QbetaBR mice revealed that a subset of the antibodies binding this epitope were of the IgG2 subclass, and therefore efficient at fixing complement, a requirement for pathogenicity of the Abs in CIA.

Amino Acid Sequence↗
PubMed1995

Hypertonic acetate dextran achieves high-flow-low-pressure resuscitation of hemorrhagic shock.

OBJECTIVE: For resuscitation of hemorrhagic hypovolemia, we compared the effectiveness of (1) isotonic lactated Ringer's solution (LRS), (2) 2400 mOsm of 7.5% NaCl:6% dextran 70 (HSD), and (3) 2400 mOsm of 7.9% sodium acetate:1.9% NaCl:6% dextran 70 (HAD). DESIGN: In six randomized, blinded experiments for each solution, conscious instrumented adult sheep were hemorrhaged by removing approximately 1.8 L (42 +/- 3 mL/kg) of blood, while maintaining the mean arterial pressure (MAP) at 50 mm Hg for 2 hours. METHODS: Test solutions were infused as needed to restore the cardiac index to baseline. RESULTS: Volume requirements with HAD (236 +/- 29 mL) and HSD (244 +/- 39 mL) were significantly less (p < 0.05) than LRS (3463 +/- 234 mL). Mean arterial pressure was normalized with HSD and LRS, but not with HAD, which resulted in MAPs of 20 to 25 mm Hg less than baseline resulting from a reduced peripheral resistance. Oxygen delivery, however, was significantly higher with HAD during the resuscitation period. Acid-base balance (pH) and oxygen consumption were normalized within 5 minutes of infusion only with HAD. CONCLUSIONS: Small-volume infusion with HAD resulting in "high-flow-low-pressure" resuscitation may offer unique hemodynamic and metabolic advantages for the initial treatment of hemorrhage from trauma.

Acetates↗
PubMed1995

Limiting initial resuscitation of uncontrolled hemorrhage reduces internal bleeding and subsequent volume requirements.

We tested the hypothesis that full or "standard resuscitation" (SR) with lactated Ringer's solution (LRS) results in increased bleeding in uncontrolled hemorrhagic shock, compared with a "limited prehospital resuscitation" (LPR) regimen and a control group of "no resuscitation" (NR). Cardiac output was used as physiological endpoint for resuscitation. Twenty swine had 25 mL/kg of blood withdrawn during a 30-minute controlled hemorrhage, followed by a 20-minute "prehospital" resuscitation regimen was conducted in three groups: the SR group (n = 6), LRS infused as needed to restore cardiac index (CI) to 100% baseline; the LPR group (n = 8), with resuscitation using LRS to 60% of baseline CI, with volume limited to 10 mL/kg; and the NR group (n = 6). After aortotomy repair, intraoperative resuscitation was continued for 120 minutes using LRS to achieve and maintain 80% of baseline mean arterial pressure. Blood pressure and cardiac index were greatly reduced, to 34% and 39% of baseline, respectively, by hemorrhage. During prehospital resuscitation, the SR group required 48.8 +/- 6.5 mL/kg of LRS, whereas the LPR group received 9.4 +/- 0.6 mL/kg (p < 0.05). Mean arterial pressure increased in all three groups during prehospital resuscitation (p < 0.05). Pulse pressures increased in the SR and LPR groups only (p < 0.05). The increment in oxygen delivery was significantly greater in the SR group, compared with the LPR group (p < 0.05), which in turn was significantly greater than the NR group (p < 0.05). Peritoneal blood volume was significantly higher in the SR group (20.6 +/- 5.6 mL/kg), versus the LPR (7.3 +/- 1.3 mL/kg; p < 0.05) and NR groups (3.0 +/- 0.9 mL/kg; p < 0.05). Crystalloid and whole blood requirements during the intraoperative resuscitation phase were significantly higher in the SR group (193 +/- 16.0 and 9.0 +/- 2.5 mL/kg), than in LPR (111.8 +/- 15.6 and 4.5 +/- 1.8 mL/kg; p < 0.05) and NR groups (128.5 +/- 32.3 and 3.9 +/- 2.3 mL/kg; p < 0.05). In the presence of uncontrolled hemorrhagic shock, LPR and NR can significantly reduce internal hemorrhage and subsequent intraoperative crystalloid and blood requirements.

Animals↗
PubMed1994

A case of germinal center formation by CD45RO T and CD20 B lymphocytes in rheumatoid arthritic subchondral bone: proposal for a two-compartment model of immune-mediated disease with implications for immunotherapeutic strategies.

In rheumatoid arthritis (RA) disease activity occurring as joint destruction of cartilage and bone is thought to be driven by inflammatory reactions which are initiated by exogenous microbial mechanisms and perpetuated by endogenous autoimmune mechanisms. According to the synovial model of RA, these reactions originate in the adjacent synovial tissues. The following set of observations is presented herein to suggest an alternate model involving subchondral bone. Lymphocytic infiltrates accompanied by immunoglobulin deposits were identified in rheumatoid subchondral bone near areas of cartilage undergoing destruction by local subchondral inflammation. CD45RO T lymphocytes also were identified with these infiltrates as well as with CD20 B lymphocytes in an area of subchondral bone containing a well-organized germinal center. Analysis of extracts of rheumatoid subchondral bone revealed a high incidence of autoantibodies directed against type II collagen, the major protein constituent of cartilaginous tissue. Analysis of IgG subclass and cyanogen bromide peptide specificity revealed a pathogenic subset of these autoantibodies. A passive transfer study utilizing similar antibodies from collagen arthritic animals confirmed that such autoantibodies would have the potential of contributing directly to disease activity observed in rheumatoid subchondral bone. These studies suggest that (i) subchondral bone may be playing an active role in RA as a local site of immune-mediated disease activity and (ii) basic and therapeutic studies aimed at understanding and eventually controlling RA should be diversified to include the study of not only synovial tissue, but also subchondral bone as a local source of the antigenic, cellular, and humoral immune components of joint destruction.

Antibody Specificity↗
PubMed1992

Collagen-induced arthritis in rats. Examination of the epitope specificities of circulating and cartilage-bound antibodies produced by outbred and inbred rats using cyanogen bromide-derived peptides purified from heterologous and homologous type II collagens.

To determine the number and location of antibody binding epitopes on type II collagen, outbred and inbred rats were immunized with chick, bovine, human, and rat type II collagen (CII, BII, HII, and RII); all sera were assayed for reaction with a panel of CB peptides purified and renatured from the immunizing collagen and from RII. Antibody reaction patterns (profiles) varied among individual outbred rats but were essentially constant over time and changed little after boosting. The strongest antibody reactions were to CB11, CB9-7, and CB12 followed by CB8, CB10, and CB6. Antibody profiles varied depending on the species of collagen used for immunization and the strain of rat immunized. Except for CB10, where antibodies were largely specific for heterologous collagens, antibodies reactive with all other CB peptides cross-reacted strongly with renatured rat CB peptides. Sera from inbred BB rats immunized with BII, CII, or HII reacted best with CB11, unlike antisera to RII that reacted strongly with CB9-7. Inbred LEW, COP, WKY, F344, and BUF rats immunized with BII reacted strongest with CB9-7 and variably with CB11 and CB12. BBxLEW F1 hybrid rats reacted almost equally with CB11 and CB9-7 producing an antibody profile intermediate to those elicited in the parent strains. Finally, antibodies reactive with rat CB11, CB9-7, and CB12 could be eluted from normal rat cartilage incubated in anti-BII serum; antibody eluate profiles generally paralleled the profile produced by the sera applied to cartilage. Taken together, these findings indicate that multiple antibody-reactive epitopes on type II collagen may be instrumental in the initiation of collagen-induced arthritis in rats, particularly shared or cross-reactive epitopes located within CB11, CB9-7, CB12, and CB8.

Animals↗
PubMed1991

Immunity to type XI collagen in mice. Evidence that the alpha 3(XI) chain of type XI collagen and the alpha 1(II) chain of type II collagen share arthritogenic determinants and induce arthritis in DBA/1 mice.

To determine whether native bovine type XI collagen (BXI) is arthritogenic, five strains of inbred mice were immunized with BXI/CFA. Arthritis was not observed in any of these strains, though it was prevalent in DBA/1 and B10.RIII controls immunized with bovine type II collagen (BII). Antisera from BXI-immunized mice reacted with mouse type XI collagen (MsXI), weakly with the alpha-chains of BXI, and minimally with mouse type II collagen (MsII). However, antisera to BII reacted with MsII and MsXI, indicating antibodies to conformation-independent epitopes shared by alpha 1(II) and alpha 3(XI). Mice immunized with BXI containing a small amount of BII developed arthritis much like those immunized with BII; sera from these mice reacted with MsXI and MsII. Delayed-type hypersensitivity responses differed from IgG responses, i.e., BXI elicited responses to alpha 1(XI), alpha 2(XI), alpha 3(XI), and alpha 1(II); BII, to alpha 3(XI) and alpha 1(II) exclusively. To determine whether alpha 1(XI), alpha 2(XI), alpha 3(XI), and alpha 1(II) are arthritogenic, DBA/1J mice were immunized with each alpha-chain. Arthritis was seen in mice injected with alpha 3(XI) or alpha 1(II). Sera to both alpha-chains reacted similarly with MsII and peptide fragment alpha 1(II)-CB11. Epitope mapping using polyclonal and mAb to type II collagen revealed that all polyclonal and 11 of 14 mAb reacted with alpha 3(XI) and alpha 1(II), whereas three mAb reacted only with alpha 1(II). In conclusion, BXI is immunogenic but not arthritogenic in five strains of mice, whereas alpha 3(XI) and alpha 1(II) are arthritogenic and immunogenic in DBA/1 mice and share greater than or equal to 11 epitopes recognized by autoantibody.

Animals↗
PubMed1991

SWR mice are resistant to collagen-induced arthritis but produce potentially arthritogenic antibodies.

SWR mice are resistant to collagen-induced arthritis but produce antibodies to type II collagen. To determine if these antibodies have arthritogenic potential, serum from collagen-immunized mice was concentrated and passively transferred to DBA/1 mice. The recipients developed severe arthritis within 72 hours. To evaluate the role of complement, SWR mice were bred with congenic inbred B10.D2/oSn (complement deficient) and B10.D2/nSn (complement normal) mice. Collagen-immunized (SWR x B10.D2/nSn)F1 mice had high levels of C5 and were susceptible to arthritis, while (SWR x B10.D2/oSn)F1 mice were deficient in C5 and were resistant to arthritis.

Animals↗
PubMed1990

Human HLA-DR beta gene hypervariable region homology in the biobreeding BB rat: selection of the diabetic-resistant subline as a rheumatoid arthritis research tool to characterize the immunopathologic response to human type II collagen.

Collagen arthritis (CA), an autoimmune model of rheumatoid arthritis (RA), has been studied in various animals. However, it has not been studied in an animal with a genetic background relevant to RA. We selected rats from a diabetic-resistant (DR) subline of the diabetic BB rat because they have an autoimmune disease-prone background, but not the immunodeficiencies of the diabetic BB rat, and the third hypervariable region (HVRIII) of the BB RT1.D beta gene appeared to encode a nucleotide sequence of the human HLA DR beta gene, which has been reported to be associated with susceptibility to RA. We synthesized oligonucleotide primers flanking the RT1.D beta HVRIII, cloned polymerase chain reaction-amplified DNA into M13mp18, and confirmed the presence of the susceptibility sequence (SS) (RRRAA) by the dideoxy sequencing method in a colony of DR BB/Wor-UTM rats. When immunized with human type II collagen (CII) in incomplete Freunds adjuvant (IFA), arthritis developed rapidly by day 10 with 100% incidence. Light and electron microscopy revealed an unusually severe and aggressive, bidirectional pattern of cartilage resorption by synovial and subchondral mononuclear and multinucleated inflammatory cells. These findings coincided with a predominant humoral response to the cyanogen bromide (CB) 11 fragment of the human CII molecule by the pathogenic IgG2a isotype. This study provides further support to the role of CA as a relevant RA model, the specific roles of the CB11 fragment as a major site of arthritogenic epitopes, and of antibody mechanisms in the pathogenesis of CA. Furthermore, the identification of an RA SS in an immune response gene of the DR BB rat presents a novel opportunity to determine with an animal model the role of other antigens as well as this SS in RA.

Amino Acid Sequence↗
PubMed1988

Collagen autoimmunity and arthritis.

Collagen-induced arthritis in animals is an example of polyarthritis that sufficiently resembles human rheumatoid arthritis to be used as a model. It is caused by immunizing susceptible animals with type II collagen isolated from articular cartilage. Susceptibility is genetically determined and linked to the major histocompatibility locus. It is important because some human arthritis is also associated with major histocompatibility genes and may be caused or aggravated by the presence of autoimmunity to normal cartilage components. Collagen-induced arthritis is also important because it is an example of immunologically mediated joint destruction, which may share some of the mechanisms present in human disease. Although it is caused by autoimmunity to collagen, susceptibility and responsiveness to type II collagen are not completely correlated, and there are examples of animals with high levels of collagen immunity who do not develop arthritis. The initial lesion appears to be the deposition of an antibody on the surface of articular cartilage, which precedes development of overt arthritis by several days. Disease can be readily transferred with specific antibody. Arthritogenic antibodies appear to have restricted epitope specificity, which may partially explain the disparities between responsiveness to immunization with collagen and susceptibility to arthritis, but precise delineation of the epitopes involved has not yet been accomplished. Complement activation also appears to be intimately involved since the disease correlates with the presence of high levels of complement-binding IgG isotypes, and passive transfer is possible only into complement-sufficient recipients. Inflammation progresses rapidly so that cartilage destruction and marginal erosion develop over a period of a few days. Collagen-induced arthritis offers a unique opportunity to study autoimmune-mediated arthritis in which the inducing antigen is well characterized and readily available. Analysis of the disease has permitted the proposal of a schema for its pathogenesis.

Animals↗