Comparison of arthritis characteristics in lowland Gorilla gorilla and mountain Gorilla beringei.код для вставкиСкачать
American Journal of Primatology 66:205–218 (2005) RESEARCH ARTICLE Comparison of Arthritis Characteristics in Lowland Gorilla gorilla and Mountain Gorilla beringei BRUCE M. ROTHSCHILD1–5n and FRANK J. RÜHLI6,7 1 Arthritis Center of Northeast Ohio, Youngstown, Ohio 2 Department of Medicine, Northeast Ohio Universities College of Medicine, Rootstown, Ohio 3 Department of Biomedical Engineering, University of Akron, Akron, Ohio 4 Division of Earth Sciences, Carnegie Institute, Pittsburgh, Pennsylvania 5 Kansas University Museum of Natural History, Lawrence, Kansas 6 Clinical Paleopathology Team, Orthopaedic University Clinic Balgrist and Institute for the History of Medicine, University of Zurich, Zurich, Switzerland 7 Institute of Anatomy, University of Zurich, Zurich, Switzerland Gorilla gorilla and the less-studied G. beringei occupy very different, geographically separate habitats. We studied the occurrence of various forms of arthritis to examine possible nature/nurture causality. The macerated skeletons of 38 G. beringei and 99 G. gorilla individuals were examined macroscopically for the presence of articular and osseous pathologies. Contrasting with only isolated osteoarthritis and infectious arthritis was the frequent occurrence of a form of erosive arthritis associated with joint fusion. Twenty-one percent of the G. beringei and 20% of G. gorilla specimens were afflicted, which are statistically indistinguishable frequencies. While both had prominent axial disease, they differed in patterns of peripheral arthritis. Whereas G. beringei showed a pauciarticular pattern, the pattern in G. gorilla was more often polyarticular. Susceptibility to spondyloarthropathy was apparently genetically imprinted before Gorilla separated into G. gorilla and G. beringei. However, the different patterns of peripheral joint involvement suggest a causality resulting from lifestyle (e.g., the presence/absence or extent of knuckle walking) or a habitat-related infectious agent. Am. J. Primatol. 66:205–218, 2005. r 2005 Wiley-Liss, Inc. Key words: spondyloarthropathy; gastroenteritis; arthritis INTRODUCTION The subfamily Homininae includes great apes and humans [Groves, 2001]. Gorilla gorilla and Homo sapiens vary only 1.6% in their nuclear DNA, and 8.8% in mitochondrial DNA [Meder, 2004]. This compares to 1.8% and 10.6% variations n Correspondence to: Bruce M. Rothschild, M.D., Arthritis Center of Northeast Ohio, 5500 Market, Youngstown, OH 44512. E-mail: email@example.com Received 1 July 2004; revised 23 October 2004; revision accepted 26 November 2004 DOI 10.1002/ajp.20139 Published online in Wiley InterScience (www.interscience.wiley.com). r 2005 Wiley-Liss, Inc. 206 / Rothschild and Rühli in G. gorilla and Pan troglodytes (chimpanzee) for nuclear and mitochondrial DNA, respectively [Hayasaka et al., 1988; Koop et al., 1989]. In 1970, Groves initially subdivided G. gorilla into three subspecies: gorilla, beringei, and graueri [Groves, 2003] Subsequently, Ruvolo et al.  and Garner and Ryder  divided Gorilla into only G. gorilla (‘‘western’’ or lowland gorilla) and G. beringei (‘‘eastern’’ or mountain gorilla), and considered graueri a subspecies of beringei. The latter classification is utilized in the present analysis (Table I). The habitats of G. gorilla (81 500 E to 181 E and 61 250 N to 51 S) and G. beringei (261 300 E to 291 450 E and 01 200 N to 31 500 S) are separated by almost 600 miles, divided by an inhospitable (to gorillas) savannah [Meder, 1993, 2004; Morgan et al., 2003]. We chose to examine arthritis patterns for a comparative study of these species, since such studies have documented reproducible patterns of disease across the mammalian spectrum [Rothschild, 1993; Rothschild & Martin, 1993; Rothschild & Rothschild, 1994, 1996a, b; Rothschild & Woods, 1989, 1991a, 1992a, b, 1996; Rothschild et al., 1993, 1994, 1997, 1998a, b, 2000]. A previous examination (by B.M.R.) of the limited number of mountain gorilla specimens scattered among North American collections suggested the occurrence of spondyloarthropathy, but there were too few available specimens to allow epidemiologic comparisons with the lowland gorilla. Since the 1900s, inflammatory arthritis has been referred to generically as rheumatoid arthritis [Rothschild & Martin, 1993]. Today the ‘‘rheumatoid’’ appellation is limited to individuals with a polyarticular, symmetrical peripheral erosive arthritis that spares the axial/central joints, such as the sacroiliac and zygapophyseal [Rothschild & Martin, 1993]. This refinement distinguishes the second major form of inflammatory arthritis, spondyloarthropathy. Spondyloarthropathy is the name given to a category of arthritis characterized by predominantly asymmetrical pauciarticular (i.e., involving less than five peripheral joints) erosive arthritis with occasional peripheral joint fusion, as well as axial joint involvement. However, despite the name, erosion and/or fusion of the central sacroiliac and vertebrae often is not present. This category of disease is divided into five varieties: reactive arthritis, psoriasis-related arthritis, inflammatory bowel disease-related arthritis, ankylosing spondylitis, and an undifferentiated form that cannot be labeled as one of the other four types. TABLE I. Characteristics Distinguishing Gorilla gorilla and Gorilla beringein Characteristic Gorilla gorilla Gorilla beringei Geography Habitat Population size Average male height Average male weight Nose Hair Silverback Arm length Preferred diet Tannin content Aggression Within groups Between groups Western Lowland 100,000 1.7 meters 140–160 kg Broader Short, brown/grey To hips and upper thighs Long Fruit Increased Eastern Mountain 3,380 1.75 meters 160–180 kg Narrower Long, black To back Short Shoots/pith Stem/bark Decreased Rare Rare Rare Common n Derived from Bradley et al. ; Calvert ; Meder [1993, 2004]; Morgan et al. . Gorilla Spondyloarthropathy / 207 Ankylosing spondylitis is a subgroup of spondyloarthropathy in which central joint involvement predominates. Involvement uniformly ascends the vertebral column over time, to eventually produce a frozen spine that mimics in appearance a bamboo plant stem. Peripheral erosive disease is quite rare. Vertebral bridging occurs by calcification of the outer layer of the intervertebral disk or anulus fibrosus; the vertebral bodies, starting with the lower lumbar, are thus smoothly united. One variety that mirrors this form of spondyloarthropathy is that caused by inflammatory bowel disease (e.g., ulcerative colitis and Crohn’s disease). Twenty percent of humans with inflammatory bowel disease develop spondyloarthropathy, which is indistinguishable in its osseous manifestations from ankylosing spondylitis. Peripheral joint erosions are rare in both. The hyperplastic skin condition referred to as ‘‘psoriasis’’ is often complicated by inflammatory arthritis. This is perhaps the most complicated form of spondyloarthropathy, because psoriatic arthritis itself can be subdivided into five varieties according to the distribution of the associated peripheral arthritis. While the character of associated central joint involvement can mirror that seen in ankylosing spondylitis, it is variable in the vertebral column distribution, and frequently and preferentially targets the cervical vertebrae. The anulus fibrosus bridging in psoriatic arthritis is often associated with exuberant new bone formation, and produces a bulky bridge rather than the smooth, continuous calcification seen in ankylosing spondylitis. An exuberant bone reaction, especially at sites involving tendon, ligament, or joint capsule insertion into bone, is frequently found in all forms of spondyloarthropathy, especially in psoriatic arthritis and the fourth form of spondyloarthropathy: reactive arthritis. Since these areas of insertion are entheses, the terms ‘‘enthesial’’ and ‘‘enthesitis’’ are applied to the bone reactions that affect such regions. This fourth type of spondyloarthropathy was previously referred to as Reiter’s syndrome. However, because of the controversy regarding the wartime behavior of the person for whom the disease was originally named, the term ‘‘reactive arthritis’’ is now preferred. The word ‘‘reactive’’ emphasizes the fact that there is an exaggerated tendency toward new bone formation, which is a reaction to bacterial challenge. The term ‘‘challenge’’ is used because this is not the result of direct bacterial invasion and/or growth in the joint, but rather a phenomenon that occurs subsequent to resolution of the infection itself. Analogously to Streptococcus-derived rheumatic fever, reactive arthritis complicates infectious agent diarrhea and certain sexually derived infections. The extent and severity of spondyloarthropathy appeared to be less significant in mountain gorillas than in their lowland counterparts. Therefore, we were interested in studying a significant sample of both gorilla species to ascertain the true population frequency of spondyloarthropathy in the mountain gorilla, and to assess the perception that the disorder is less severe in the mountain gorilla. The current study was undertaken to contrast mountain and lowland gorillas in terms of the frequency and character of reactive arthritis present in each species, and to utilize behavioral differences to predict which pathway organisms are responsible for this condition. MATERIALS AND METHODS The complete articular skeletons of adult gorillas (G. gorilla and G. beringei) were examined [Meder, 2004]. Only individuals with fused epiphyses were 208 / Rothschild and Rühli included in the sample. We compared specimens of G. beringei (mountain gorilla), from the Musée Royal de l’Afrique Centrale (Tervuren, Belgium), with specimens of G. gorilla (lowland gorilla). The latter were obtained from the Department of Anthropology at the Cleveland Museum of Natural History and the Department of Mammology at the National Museum of Natural History (Smithsonian, Washington, D.C.), but they represent the repositories of a single collection effort [Rothschild & Woods, 1989, 1991a]. All of the samples were collected in the 1920s and 1930s from free-ranging animals shot in the wild. The G. gorilla specimens were taken from the French Cameroons in coastal West Africa, the Congo, Gabon, and Nigeria; and the G. beringei specimens were taken from the Democratic Republic of Congo. The latter, which were received by the museum in 1910–1958, were subdivided into G. b. beringei from the Uganda-Zaire border and G. b. graueri from the eastern Congo. Sex was determined on the basis of data recorded at the time the skeleton was acquired. The specimens had been previously treated with lye to remove the soft tissue. They were surveyed for macroscopic evidence of articular and periarticular joint pathology. Each skeletal element of the sampled G. beringei individuals was carefully observed by both authors (B.M.R. and F.J.R.), and the G. gorilla samples were examined by B.M.R. and Robert Woods [Rothschild & Woods, 1989]. Concurrence was obtained to ascertain erosion and rule out postmortem damage. For the purposes of this study, articulations were listed as missing if any artifactual damage precluded the demonstration of joint disease. Chi-square and Fisher’s exact tests were used to assess the frequency of spondyloarthropathy in both the species and the subspecies, and the frequencies of the various types of joint involvement. RESULTS Thirty-eight G. beringei (50% male) and 99 G. gorilla (78% male) skeletons were examined for evidence of articular or osseous pathology. Moderate to severe osteoarthritis was present in one (3%) G. beringei and eight (8%) G. gorilla specimens (Table II; Fisher’s exact test, P=0.365, n.s.). Evidence of osseous infection was present in seven (7%) G. gorilla specimens, but was not found in any of the G. beringei specimens (Table II; Fisher’s exact test, P=0.571, n.s.). In the current study we analyzed the articular manifestations in the eight G. beringei (21% of examined animals were afflicted) and 20 (20%) G. gorilla individuals with sacroiliac or erosive disease (Table II), and noted the statistically indistinguishable frequencies (w2=0.4388) in the two species. An examination of the G. beringei subspecies (b. beringei and b. graueri) revealed that five of 20 (25%) and three of 18 (17%), respectively, were affected. Since those frequencies did not differ significantly (Fisher’s exact test, P=0.2587, n.s.), and the character of the disease (e.g., pauciarticular nature and joints affected) was indistinguishable between G. b. beringei and G. b. graueri, we did not consider subspecies aspects any further in the current analyses. Among those specimens whose sex was recorded at the time of acquisition, spondyloarthropathy was equally malepredominant (Table II) in G. beringei and G. gorilla (75% and 60%, respectively). Erosions were marginal (bare area) and subchondral in distribution. The term ‘‘marginal,’’ as used herein, denotes the zone of metaphyseal bone that is within the synovial membrane but is extrinsic to the cartilage-lined bone [Resnick, 2002; Rothschild & Martin, 1993]. ‘‘Subchondral’’ refers to the portion of the articular surface that was originally covered by cartilage. All erosions were associated with the formation of new bone in a peri-erosional Gorilla Spondyloarthropathy / 209 TABLE II. Comparative Pathology in Mountain and Lowland Gorillas Character Gorilla beringei Gorilla gorilla Number examined Percent male Pathology (%) Fractures (%) Severe osteoarthritis (%) Infection (%) Spondyloarthropathy (%) Percent male Affected animal characteristics: Only sacroiliac affected (%) Peripheral joints affected (%) Pauciarticular (%) Polyarticular (%) No. affected joints Distribution (%) Shoulder Elbow Wrist Metacarpal phalangeal Proximal interphalangeal Distal interphalangeal Hip Knee Ankle Metatarsal phalangeal Interphalangeal (pedal) Sacroiliac joint 38 50 99 78 6 3 0 21 75 8 8 7 20 60 75 25 25 0 n. a. 20 80 40 40 5,6,8,10,14,15,15,21 12 0 0 0 0 0 12 12 0 0 0 100 5 20 50 70 60 25 0 15 40 50 40 10 Fig. 1. Palmar view of Gorilla gorilla metacarpals and phalanges. Erosive arthritis with reactive new bone. Note the strong enthesial reaction in the proximal phalanges. pattern (Figs. 1 and 2). The new or reactive bone, bordering the rim of the erosion, was distinct from the metaphyseal bone surrounding it. Reactive bone was recognizable as a smooth, billowy, sclerotic growth at the periphery of the resorbed lesion. 210 / Rothschild and Rühli Fig. 2. Palmar view of a G. gorilla metacarpal phalangeal joint. Subchondral erosion is prominent on the proximal phalanx. Reactive new bone formation with remodeling of the metacarpal is evident. This growth was easily distinguished from the cracked and ragged edges that are typically observed on the border of pseudo-erosions associated with artifact. In dry bone, unmagnified or under magnification of r40 , a lytic lesion, from which bone tissue has been removed by osteoclasts, presents smooth, rounded edges of any surfaces within and at the boundaries of the lesion [Leisen et al., 1987; Rothschild & Woods, 1991b; Rothschild et al., 1988]. Transitions from one plane of bone tissue to another are smoothed. The edges of all exposed trabeculae appear smoothed, while intersecting planes of dense cortical bone meet with a rounded edge. Although inflammation initially may activate osteoclastic resorption of perilesional trabeculae, it subsequently activates osteoblastic deposition in the same region [Leisen et al., l987]. Thus, any trabecular edges initially exposed at the lesion boundary by osteolysis subsequently appear thicker than trabecular edges revealed by postmortem processes in the same region. In contrast to the minimal or absent peri-erosional bone reaction noted in human rheumatoid arthritis [Rothschild et al., 1988; Woods & Rothschild, 1988], that of both species of gorillas corresponded more to the reactive bone seen in human spondyloarthropathy [Rothschild & Woods, 1991b]. New bone formation (enthesitis) at sites of tendon, ligament, and capsule (entheses) was also noted. Two patterns of arthritis were represented among the two species with regard to erosive disease affecting the peripheral joints. Peripheral joint involvement was found in 25% (2/8) of afflicted G. beringei (100%) and 80% (16/20) of afflicted G. gorilla individuals (w2=1.800, n.s.). A polyarticular pattern was found in none (0%) of the peripherally afflicted G. beringei, as compared to eight of 16 (50%) afflicted G. gorilla (w2=1.800, n.s., possibly related to sample size). Five to 21 joints (average=10) were affected in the latter. Different joints were affected (Table II) in the two species. The metatarsal phalangeal, metacarpal Gorilla Spondyloarthropathy / 211 phalangeal, and interphalangeal (both manus and pes) joints were more commonly affected in G. gorilla (w2=8.119, Po0.005). Limiting the statistical analysis to only afflicted gorillas, all eight (100%) of the afflicted G. beringei had sacroiliac erosions (Fig. 3) or fusion (Fig. 4), as compared to two of 20 (10%) G. gorilla (w2=20.160, Po0.0001). The erosions appeared as multiple small crater-shaped holes with smooth, rounded edges. Syndesmophytes (calcification in the anulus fibrosus) were present in two G. beringei (5%) (Figs. 5 and 6) and four G. gorilla (20%) specimens, and costovertebral joint fusion was observed in one individual of each species. DISCUSSION Frequency of Arthritis and Pathophysiology of Spondyloarthritis The prevalence of all forms of arthritis was indistinguishable between mountain gorilla (Gorilla bereingei) and their lowland relatives (G. gorilla), and even within subspecies of the former. This uniform frequency may be related to a uniform genetic predisposition (i.e., the possession of similar risk factors). The histocompatibility gene (HLA-B27, MHC class I) predisposes humans to spondyloarthropathy [Khare et al., 1998; Schlosstein et al., 1973]. Several hypotheses have been offered to explain this, including a role in antigen presentation, CD8 T (suppressor) cell modulation, and molecular mimicry (antigenic similarities between the host tissue and enteropathic bacteria) [Allen et al., 1999; Burmester et al., 1995]. Insertion into rats with a gene sequence coding for HLA-B27 demonstrated that this predisposition to spondyloarthropathy is transpecific [Zhou et al., 1998]. HLA-B27 is unique among MHC class I molecules because it possesses a deep ‘‘B’’ pocket or epitope that allows binding of bulky, positively charged (because of Fig. 3. ‘‘En face’’ view of the auricular portion of a G. gorilla sacroiliac joint. Erosions can be seen throughout the auricular surface. 212 / Rothschild and Rühli Fig. 4. Anterior view of a G. gorilla pelvis, showing unilateral right sacroiliac joint fusion. Note the prominent right-sided lumbar vertebral body osteophytes, with a prominent bulky left syndesmophyte at the same level. arginine at the second B-27 position) peptides [Jardetzky et al., 1991; Rammensee et al., 1995; Rötzschke et al., 1994]. There are more than 20 variations within the pocket of the B27 molecule, not all of which appear to cause a predisposition to spondyloarthropathy [Allen et al., 1999; de Castro, 1998]. In addition to the apparently mandatory second position of arginine, position 45 glutamic acid and position 67 cysteine apparently are required [Buxton et al., 1992; Rojo et al., 1993]. The occurrence of spondyloarthropathy depends not only on host susceptibility, but also on external microorganisms (in the form of infectiousagent diarrhea) [Ahvonen et al., 1969; Bardin & Lathrop, 1992; Borg et al., 1992; Buxton et al., 2002; Calin & Fries, 1976; Cohen et al., 1987; Deighton, 1993; Dworkin et al., 2001; Graham, 1919; Hannu & Leirisalo-Repo, 1988; Hannu et al., 2002; Herrlinger & Asmussen, 1992; Hughes et al., 1991; Kanakoudi-Tsakalidous et al., 1998; Kvien et al., 1994; Laasila & Leirisalo-Repo, 1999; Leino et al., 1980; Leirisalo-Repo et al., 1997; Locht & Krogfelt, 2002; Locht et al., 1993, 2002; MakiIkola & Granfors, 1992; Maximov et al., 1992; Merilahti-Palo et al., 1991; Putterman & Rubinow, 1993; Rudwaleit et al., 2001; Simon et al., 1981; Solitar et al., 1998; Stein et al., 1980; Taccetti et al., 1994; Thomson et al., 1994, 1995; Tupchong et al., 1999; Yli-Kerttula et al., 1995]. Of note is the contraction of spondyloarthropathy by 20–30% in individuals who develop Shigella dysentery, if they possess HLA-B27. This contrasts with a frequency of 0.25% if they do not [Keat, 1988]. It has been suggested that 60–80% of human individuals with at least the reactive form of spondyloarthropathy have HLA-B27, an allele that is present in 8–13% of Caucasian populations [Märker-Hermann et al., 2004]. Gorillas have HLA-A, B, and C loci, but do not have a specific histocompatibility equivalent to human HLA-B27 [Lawler et al., 1991; Watkins et al., 1991]. Gorilla Spondyloarthropathy / 213 They do, however, have a region with partial sequence and functional homology [Urvater et al., 2001]. That sequence is not relatable to the sequence of human HLA-B27, but only to the epitope (the focal site in which binding of the abovementioned molecules occurs). While systematic screening of gorillas to assess the frequency of this epitope has not been completed, almost all specimens examined to date (lowland G. gorilla, independently of spondyloarthropathy affliction) have had this epitope [Urvater et al., 2001]. The gorilla epitope most similar to HLAB27 was labeled Gogo B01. Gogo B0101 differs from HLA-Bn1513 by 21 residues, and from HLA-Bn2702 by 22 residues [Urvater et al., 2001]. Most (15) of the differences occurred in the peptide binding region, the polymorphic alpha-1 and alpha-2 domains. Residues 71–90 of the alpha-1 domain are identical to HLABn2702, a sequence that is not unique to HLA-B27 in humans, and is not even conserved among all types of human B27, such as 2705. Substitutions of methionine (for glutamic acid at position 45) and serine (for cysteine at position 67) are noted in Gogo B01 (contrasted with B27). Such substitutions in human B27 significantly decrease arginine peptide binding. They shrink the epitope pocket size and change the charge from negative to neutral. Such a modification usually interferes with binding and thus with susceptibility to spondyloarthropathy. Character of Arthritis The G. beringei and G. gorilla specimens differed significantly in terms of skeletal distribution and severity of erosive peripheral disease. This represents an unusual phenomenon in data-based skeletal analysis, and is similar only to previous observations in Pan (Rothschild and Rühli, 2005, this issue). The reproducibility of disease characteristics across mammalian species lines has been clearly documented for spondyloarthropathy [Rothschild, 1993; Rothschild & Martin, 1993; Rothschild & Rothschild, 1994, 1996a, b; Rothschild & Woods, 1989, 1991a, 1992a, b, 1996; Rothschild et al., 1993, 1994, 1997, 1998a, b, 2000]. The severity may vary, but the skeletal distribution is reproducible. Population frequency has shown significant variation over time in a number of species, but apparently is independent of geography [Rothschild & Rothschild, 1993, 1996a, b; Rothschild & Woods, 1992c]. Gorillas appear to differ in terms of the character of the resultant arthritis, rather than in susceptibility. Is this a manifestation of habitat? Does the high frequency of hand involvement in lowland gorillas (apparently related to knuckle walking) reflect the absence of knuckle walking in mountain gorillas [Bradley et al., 2004; Tuttle & Watts, 1985]? Enthesitis was equally represented in both groups, implying that activity levels probably did not differ much between the species [Shaibani et al., 1993]. Thus, another factor may be more significant: Spondyloarthropathy is a type of arthritis that is inducible by infectious-agent diarrhea [Resnick, 2002; Rothschild & Martin, 1993]. Several enteropathic organisms have been recognized as playing a role in this disease, and have been associated with specific joint distributions and ancillary abnormalities. Perhaps the difference between mountain and lowland gorillas can be explained by the presence of different habitat-related pathogens. Escherichia coli, Salmonella, Campylobacter, Streptococcus pyogenes, Yersinia, Shigella, Clostridium difficile, and Giardia lambdia can all cause infectiousagent diarrhea and spondyloarthropathy in humans [Ahvonen et al., 1969; Bardin & Lathrop, 1992; Borg et al., 1992; Buxton et al., 2002; Calin & Fries, 1976; Cohen et al., 1987; Deighton, 1993; Dworkin et al., 2001; Graham, 1919; Hannu & 214 / Rothschild and Rühli Fig. 5. Anterior view of a G. beringei pelvis and lumbar vertebrae, showing partial sacroiliac joint fusion and prominent syndesmophytes. Leirisalo-Repo, 1988; Hannu et al., 2002; Herrlinger & Asmussen, 1992; Hughes et al., 1991; Kanakoudi-Tsakalidous et al., 1998; Kvien et al., 1994; Laasila & Leirisalo-Repo, 1999; Leino et al., 1980; Leirisalo-Repo et al., 1997; Locht & Krogfelt, 2002; Locht et al., 1993, 2002; Maki-Ikola & Granfors, 1992; Maximov et al., 1992; Merilahti-Palo et al., 1991; Putterman & Rubinow, 1993; Rudwaleit et al., 2001; Simon et al., 1981; Solitar et al., 1998; Stein et al., 1980; Taccetti et al., 1994; Thomson et al., 1994, 1995; Tupchong et al., 1999; Yli-Kerttula et al., 1995]. Escherichia coli, Salmonella, Campylobacter, S. pyogenes, C. difficile, and G. lambdia all cause a predominantly polyarticular arthritis, while pauciarticular disease is caused by Yersinia and Shigella. We suggest that there are identical susceptibility, but different ‘‘precipitating’’ organisms in G. gorilla and G. bereingei, and that Shigella or Yersinia is the likely infecting agent in G. bereingei (as it is in Pan paniscus (Rothschild and Rühli, submitted)). The notion that exposure to an infecting organism, rather than species specificity, is the important factor in these findings is supported by a comparison of wild-caught and zoological park-derived G. gorilla individuals. The pattern of arthritis in wild-caught gorillas is polyarticular, suggesting a possible role for E. coli, Salmonella, Campylobacter, S. pyogenes, C. difficile, or G. lambdia. Shigella is well recognized as the stimulus for spondyloarthropathy in Gorilla Spondyloarthropathy / 215 Fig. 6. Anterior oblique view of a G. beringei lumbar spine, showing syndesmophytes effacing disk space visibility, and zygapophyseal (facet) joint fusion. captive G. gorilla individuals, which manifest a pauciarticular pattern of arthritis [Neiffer et al., 2000; Raphael et al., 1995], producing a pauciarticular pattern of arthritis. Thus the pattern is habitat-specific, rather than species-specific. A similarity between bacterial contamination in zoo and natural Gorilla bereingei habitats is suggested. Gorilla habitats include primary and secondary rain forest, swamp forest, montane forest, and marshy clearings (bais) [Meder, 2004]. The speculation that tannin (which is increased in the diet of G. gorilla [Calvert, 1985]) binds excess dietary iron or helps to maintain a healthy population of gut microbes [Remis, 2001] may be pertinent to the issue of which microorganisms precipitate spondyloarthropathy. 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