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Poster Session 2. SLE: Antiphospholipid syndrome79

186.MYCOPHENOLATE MOFETIL: A POTENTIAL TREATMENT FOR

REDUCING PROTEINURIA ASSOCIATED WITH MEMBRANOUS LUPUS

NEPHRITIS

ML Ferro, MY Karim, IC Abbs, DP D'Cruz, MA Khamashta, GRV Hughes. The Lupus Research Unit, The Rayne Institute, St Thomas' Hospital,

London, United Kingdom

Background:Membranous glomerulonephritis is the most common primary cause of adult nephrotic syndrome. In SLE it represents10-15% of the spec- trum of lupus nephritis. The natural evolution of the disease and treatment in SLE remains controversial and significant proteinuria despite treatment is common. Mycophenolate Mofetil (MMF) is an effective immunosuppressive agent in solid organ transplantation and has recently proved to be effective in patients with refractory lupus nephritis. Methods:In an open study we prospectively assessed 10 patients with SLE (meeting the ACR classification criteria) with biopsy proven WHO Class V membranous nephritis, previously resistant or intolerant to prednisolone, cy- clophosphamide and azathioprine. MMF was commenced (0.25 - 2 g daily) and disease activity was measured with the SLEDAI score. Patients were followed for at least one year. Results:Nine patients were female, their mean age was 35yrs and racial distribution: 5 Caucasian, 3 Asian and 2 Afro-Caribbean. In nine patients the mean SLEDAI improved significantly from 10.7 at baseline to 2.6 at follow-up, and stable urea and creatinine values were maintained. 24 hour proteinuria decreased significantly. At baseline, two had nephrotic range proteinuria (>

3.5 g/day), four had significant proteinuria (1.5- 3.4 g/day) and four had mild

proteinuria 0.5 - 1.4g/day. At follow-up, only one patient had mild protein- uria 0.5 - 1.4g/day. At follow-up, the mean serum urea was 5mmol/l; mean creatinine: 76mmol/l; mean GFR measured by Cr EDTA: 80 mls/min. MMF was well tolerated with only one patient suffering a mild reversible thrombo- cytopenia. Conclusions:MMF is a potentially useful immunosuppressive agent in con- trolling the proteinuria associated with membranous lupus nephritis and larger studies are warranted.SLE: Antiphospholipid syndrome

187.HEADACHE IN SLE: IS IT ASSOCIATED WITH THE PRESENCE OF

ANTIPHOSPHOLIPID ANTIBODIES?G Sanna, MJ Cuadrado, ML Bertolaccini, MA Khamashta, GRV Hughes. Lupus Research Unit, The Rayne Institute, St Thomas' Hospital, London,

United Kingdom

Background:Headache is a frequent complaint in patients with systemic lupus erythematosus (SLE) but its real prevalence and association with an- tiphospholipid antibodies (aPL) is still unclear. We designed this study to as- sess the frequency and type of headache in SLE and its possible association with the presence of aPL. Methods:This study included 323 patients fulfilling at least 4 of the 1982 ACR criteria for SLE (308 female, mean age 41.9±12.6 years, mean disease duration 10.9±7.9 years). All clinical and serological data were retrospec- tively reviewed and patients were also interviewed for a better accuracy of the data. IgG and IgM anticardiolipin antibodies (aCL) were detected by stan- dard ELISA. Lupus anticoagulant (LA) was screened using activated partial thromboplastine time and dilute Russell's viper venom time, and confirmed according to the guidelines recommended by the Subcommittee on Lupus

Anticoagulant/Phospholipid dependent Antibodies.

Results:Headache was present in 78 patients (24%). Of these, 35 patients (10.8%) had tension type headache, 34 (10.5%) had migraine, 4 (1.2%) intractable/non-specific headache, 3 (0.9%) cluster headache, and 2 (0.6%) headache due to intracranial hypertension. aPL were present in 127 patients (39.3%). Of these, 89 presented aCL (61 IgG, 15 IgM and 13 both isotypes IgG and IgM). LA was present in 69 patients. aCL were more frequently found in patients with headache than in those without (37% vs. 24.5%, RR 1.5 [95% CI 1.0-2.3], p=0.04). IgG aCL was the only isotype associ- ated with headache, with a frequency significantly increased in patients with this manifestation than in those without (32% vs. 20%, RR 1.6 [95% CI 1.1-

2.4], p=0.03). The prevalence of IgM aCL was not different among patients

with/without headache. Although the prevalence of LA was higher in patients with headache than in those without (29.4% vs. 18.7%), the difference was not statistically significant. When patients with headache were subdivided into different subtypes, we found no associations between the presence of either of them and aPL.Conclusions:Headache is frequent in SLE, being the tension type and migraine the most prevalent. The presence of aCL, particularly of the IgG isotype may be a marker of headache as a whole, but was not specifically associated with any subtype of headache.188.ANTIPHOSPHOLIPID ANTIBODIES IN LUPUS PATIENTS WITH

SEIZURES: PREVALENCE AND CLINICAL SIGNIFICANCE

G Sanna, ML Bertolaccini, MJ Cuadrado, MA Khamashta, GRV Hughes. Lupus Research Unit, The Rayne Institute, St Thomas' Hospital, London,

United Kingdom

Background:Seizure disorders are frequent in patients with systemic lupus erythematosus (SLE) with a prevalence of around 5-10%. An association with antiphospholipid antibodies (aPL) has been reported by our group. We designed this study to assess the frequency and type of seizures in a large cohort of SLE patients and its possible association with the presence of aPL. Methods:This study included 323 patients, all fulfilling at least 4 of the 1982 ACR criteria for SLE (308 female, mean age 41.9±12.6 years, mean disease duration 10.9±7.9 years). All clinical and serological data were retrospec- tively reviewed and patients were also interviewed for a better accuracy of the data. IgG and IgM anticardiolipin antibodies (aCL) were detected by standard ELISA. LA was screened using activated partial thromboplastine time and di- lute Russell's viper venom time, and confirmed according to the guidelines recommended by the Subcommittee on Lupus Anticoagulant/Phospholipid dependent Antibodies. Results:Seizures were present in 27/323 patients (8.3%). Of these, 16 pa- tients (5%) had partial or focal (PS) and 10 (3.1%) generalized seizures (GS). One case is still under investigation. Nine out of 27 patients (33%) had concomitant cerebrovascular disease (CVD): 5 had stroke, 3 TIAs and

1 sinus thrombosis. aPL were found in 127/323 patients (39.3%). Of these,

61 patients had IgG aCL, 15 IgM, and 13 both isotypes IgG and IgM. Lupus

anticoagulant (LA) was present in 69/323 patients (21.4%). aCL were more frequent in patients with seizures than in those without (59.2% vs. 24.7%, RR 3.8 [95%CI 1.8-7.9], p=0.0004). Both IgG and IgM aCL were more fre- quently found in patients with seizures than in those without (52% vs. 20%, RR 3.6 [95%CI 1.8-7.3], p=0.0006 and 22% vs 7.5%, RR 3.0 [95%CI 1.3-

6.8], p=0.02, respectively). LA was more frequently found in patients with

seizures than in those without (25.9% vs 20.6%), but the difference was not statistically significant. Patients were subdivided in those who presented PS and those who presented GS. Patients with PS presented more frequently IgM than those without (25% vs 8%, RR 3.5 [95%CI 1.2-10.1], p=0.04). Pa- tients with GS presented more frequently IgG aCL than those without (60% vs 21.5%, RR 5.1 [95%CI 1.5-17.6], p=0.01). After excluding all patients who had concomitant CVD, the association of PS with IgM aCL and GS with IgG aCL remained significant. Conclusions:aCL are frequently found in SLE patients with seizures, sug- gesting that these antibodies may play a pathogenic role.189.METATARSAL FRACTURES IN SYSTEMIC LUPUS ERYTHEMATOSUS: POSSIBLE ASSOCIATION WITH ANTIPHOSPHOLIPID

SYNDROME

SR Sangle, DP D'Cruz, MP Khamashta, GR Hughes.Lupus Research Unit, The Rayne Institute, St Thomas' Hospital, London, United Kingdom Background:Metatarsal fractures may occur in athletes and chronic dis- orders such as osteoporosis, diabetes mellitus, chronic metabolic disorders and in patients receiving steroids. Osteoporosis is not uncommon in SLE because of the disease itself and/or steroid therapy. Objective:To describe the clinical and radiological features of patients with metatarsal fractures. Methods:We describe 11 patients with exacerbations of their lupus who subsequently developed stress/insufficiency metatarsal fractures. Ten of these patients had no history of obvious trauma and one had a trivial foot injury. Patients were reviewed for duration of their autoimmune disease, course, length and dose of steroids, auto-antibody profile, menopausal state, presence of osteoporosis, other chronic disorders, location and characteris- tics of fracture. Diagnosis was based on radiographs and/or radionucleide bone scan. Results:All patients were female with mean age 41 years. Nine of them had systemic lupus erythematosus (SLE) as classified by the ACR criteria. Two had primary antiphospholipid syndrome (APS). Seven had secondary APS (SLE +APS). Thus 9 of 11 had APS. Five patients had received prednisolone (>15 mg) for more than six months in the past. Only one had a history of a trivial foot injury while climbing down stairs. All patients were screened for metabolic, endocrine disorders and myeloma. One patient had DM type I with secondary APS. Her metabolic profile was normal and bone mineral density (BMD) was normal. Five patients had osteoporosis, one osteopenia. The

other five patients had normal BMD. One patient with primary APS showedDownloaded from https://academic.oup.com/rheumatology/article/42/suppl_1/79/1773205 by guest on 16 July 2023

80Poster Session 2. SLE: Antiphospholipid syndrome

avascular necrosis of second and third metatarsal heads. A further patient on prednisolone had bilateral avascular necrosis of femoral heads. Four of these patients had bilateral metatarsal fractures. Conclusions:Metatarsal fractures may occur in athletes and chronic dis- orders such as osteoporosis, diabetes mellitus, chronic metabolic disorders and in patients receiving steroids. Osteoporosis is not uncommon in SLE because of the disease itself and/or steroid therapy. Whilst corticosteroids may have played a role in these patients with reduced BMD, it is difficult to explain these fractures in the five patients who had normal BMD. Strikingly

9 of our patients had APS and bone micro-infarction, possibly related to an-

tiphospholipid antibodies may be an additional relevant factor.

190.LUPUS PATIENTS WITH THROMBOSIS BUT NEGATIVE FOR aCL

AND LA: IS TESTING FOR OTHER aPL HELPFUL IN THE DIAGNOSIS OF

ANTIPHOSPHOLIPID SYNDROME?

A Theodoridou, ML Bertolaccini, D D'Cruz, C Hamid, MA Khamashta,

GRV Hughes.

Lupus Research Unit, The Rayne Institute, St Thomas'

Hospital, London, United Kingdom

Background:Several authors have suggested that testing for other an- tiphospholipid antibodies may help to identify the APS in SLE patients with thrombosis but repeatedly negative for anticardiolipin antibodies (aCL) and/or lupus anticoagulant (LA). Methods:To test this hypothesis, we studied 3 groups of SLE patients: 24 female, 2 male, mean age 46±12, all with history of thrombosis (5 venous,

13 arterial and 8 both venous and arterial thrombosis) and positive for aCL

and/or LA (SLE/APS); 26 female, mean age 40±11, with no history of throm- botic events (SLE only) and 25 female, 1 male, mean age 39±11, all with history of thrombotic events (16 venous, 6 arterial and 4 both venous and arterial events) but repeatedly negative for aCL/LA (SLE-thrombosis). aCL and LA were re-tested in all samples. All patients were tested for IgG and IgM anti-β2GPI and anti-prothrombin antibodies (aPT) by in-house ELISAs. Results:Anti-β2GPI antibodies were present in 15/26 (58%) patients with SLE/APS (12 IgG and 3 IgM) and 0/26 patients with SLE only and SLE- thrombosis. aPT were present in 10/26 (38%) patients with SLE/APS (9 IgG and 1 IgM) and 1/26 (3.8%) patients with SLE only (IgG isotype) and 3/26 (11.5%) SLE-thrombosis patients (2 IgG and 1 IgM isotypes). Conclusions:Testing for aPL other than aCL and LA in patients with throm- bosis but persistently negative for aCL and LA may be helpfull in selective cases. Anti-β2GPI may not be detected in patients negative for aCL.

191.ANTIPROTHROMBIN ANTIBODIES: CLINICAL SIGNIFICANCE IN

PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS

ML Bertolaccini

1 ,TAtsumi 2 , MA Khamashta 1 ,TKoike 2 , GRV Hughes 1 1 Lupus Research Unit, The Rayne Institute, St Thomas' Hospital, London,

United Kingdom;

2 Department of Internal Medicine II, Hokkaido University

School of Medicine, Sapporo, Japan

Background:Antiprothrombin antibodies can be detected by coating pro- thrombin on irradiated plates (aPT) or using phosphatidylserine-prothrombin complex as the antigen (aPS/PT). We investigated the clinical relevance of antiprothrombin antibodies detected by these methods and analised the ef- fects of these antibodies on plasma prothrombin. Methods:IgG and IgM aPT and aPS/PT were tested in 212 SLE patients (mean age 43±12 years, mean disease duration 12.5±8.9 years). Plasma prothrombin levels were determined by a sandwich ELISA. Prothrombin ac- tivity was determined by a clotting assay. Results:aPT were found in 31% of the patients and 9% of the 100 control subjects. aPS/PT were found in 30% the patients and none from the control group. IgG aPT were more frequent in patients with thrombosis than in those without (40% vs. 19%, p=0.001). Levels of IgG aPT were also higher in pa- tients with thrombosis than in those without (p=0.0004). IgG and IgM aPS/PT were more frequent in patients with thrombosis than in those without (41% vs. 17%, p=0.0001 and 29% vs. 7%, p<0.0001, respectively). IgG and IgM aPS/PT were more frequent in patients with arterial thrombosis than in those without (38% vs. 22%, p=0.03 and 32% vs. 10%, p=0.0008) and in patients with venous thrombosis than in those without (44% vs. 20%, p=0.001 and

30% vs. 11%, p=0.004, respectively). Levels of aPS/PT were higher in pa-

tients with thrombosis than in those without (p=0.0001 for IgG and p=0.004 or IgM, respectively). The mean plasma levels of prothrombin were not dif- ferent between patients and controls (0.2±0.04mg/ml vs. 0.223±0.08mg/ml, p=0.3). Prothrombin levels were not different between patients with aPT nor with aPS/PT when compared to those without (0.17±0.04mg/ml vs.

0.205±0.04mg/ml, p=0.2 and 0.19±0.51mg/ml vs. 0.2±0.22mg/ml, p=0.7;

respectively). Prothrombin activity was not different between SLE patients and controls nor between SLE with/without aPT or aPS/PT. Conclusions:aPT and aPS/PT are frequent in SLE. Their presence asso-

ciates with APS manifestations. These antibodies seem not to interfere withprothrombin in plasma since its level/activity is not different between patients

with/without the antibodies.

192.THE VALUE OF ANTI-PROTEIN S ANTIBODIES IN LUPUS PATIENTS

ML Bertolaccini, G Sanna, S Ralhan, LC Gennari, MA Khamashta,

GRV Hughes.

Lupus Research Unit, The Rayne Institute, St Thomas'

Hospital, London, United Kingdom

Background:Protein S is a plasma protein, critical component of the antico- agulant activity of protein C. As antibodies directed against protein S (anti- ProtS) may be involved in the development of thrombosis in patients with the antiphospholipid syndrome, we designed this study to assess the preva- lence, immunological characteristics and clinical significance of anti-ProtS. Methods:This study comprised 184 patients, all fulfilling>4oftheACRcri- teria for the classification of SLE. All patients were tested for IgG anti-ProtS by an in-house ELISA. Anti-ProtS were also analised in 119 patients with obstetric history available, all of whom have been pregnant at least once. Ninety-nine healthy donors comprised the control group. Plasma levels and functional activity of protein S were tested by ELISA (Asserachrom Free Pro- tein S) and a coagulation test (IL Test TM Protein S), respectively. Results:57 SLE patients (31%), and 4 healthy controls (4%) were posi- tive for IgG anti-ProtS (mean + 3SD). Patients with thrombosis presented IgG anti-ProtS more frequently than controls (29% vs 4%, OR 9.5 [95% CI

3.07-29.3], p<0.0001). Anti-ProtS were more frequent in patients with ve-

nous thrombosis and in those with arterial thrombosis, than in controls (41% vs. 4%, OR 16.5 [95% CI 5-54], p<0.0001 and 23% vs. 4%, OR 7 [95%CI

2.1-23.5], p=0.0008, respectively). Anti-ProtS were present 39/119 (33%)

patients with obstetric history available. Patients with pregnancy morbidity presented anti-ProtS more frequently than the control group (24% vs. 4%, OR 7.9 [95% CI 2.3-28], p=0.0009). When subdividing the patients into sub- groups, those with miscarriages and/or fetal death presented anti-PS much more frequently than the controls (24% and 18% vs. 4%, OR 7.6 [95% CI

2.1-27], p=0.0017 and OR 5.4 [95% CI 1.3-22], p=0.021, respectively). Pa-

tients with prematurity, preeclampsia and intra-uterine growth restriction pre- sented anti-PS more frequently than the control group (36%, 47% and 44% vs. 4%; OR 13.6 [95% CI 2.8-66], p=0.003, OR 21 [95% CI 5-86], p<0.0001 and OR 19 [95% CI 4-99], p=0.0014, respectively). Plasma levels of free protein S were not statistically different between patients with and without anti-ProtS and controls (68.1±28.1% vs. 77.39±16.5% vs. 84.5±15.3%, re- spectively). Protein S functional activity was also not different between sub- groups (120±53% in anti-ProtS positive vs. 138.2±52% in anti-ProtS nega- tive vs. 132.3±36% in controls). Conclusions:Anti-ProtS are frequent in SLE patients. Their presence is more frequent in patients with thrombosis and pregnancy morbidity. These antibodies seem not to interfere with free protein S in plasma since its level and/or functional activity are not impaired. Further studies including larger populations are needed to elucidate the real value of anti-protS.

193.ANTIBETA 2 GLYCOPROTEIN ANTIBODIES IN PATIENTS WITH SLE

AND ANTIPHOSPHOLIPID SYNDROME; RELATION TO CLINICAL

MANIFESTATIONS IN EGYPTIAN PATIENTS

WF El Bazz

1 , AF El Ghobarey 2 , M Abdulhafeez 3 1

Department of Internal

Medicine and Rheumatology, Al Azhar University, Cairo, Cairo, Egypt; 2 Department of Internal Medicine and Rheumatology, Faculty of Medicine,

Al Azhar University, Cairo, Cairo, Egypt;

3

Department of Rheumatology,

Maadi Armed Force Hospital, Cairo, Cairo, Egypt

Background:Anti B2 GP1 is a cofactor during the formation of anticardi- olipin antibodies in phospholipid membrane of different tissues and causing injury of tissues in antiphospholipid antibody syndrome. Methods:Anti B2 GP1 antibodies were tested for its prevalence in 40 Egyp- tian patients with SLE and 20 with APS Results:The main clinical manifestation in Egyptian SLE patients were arthritis (87.5%), photosensitivity (75%), alopecia (70%), malar rash (57.5%), Raynoud's phenomenon (57.5%), oral ulcers (45%), polyserositis (22.5%), cerebral lupus (15%), repeated abortion (11.4%), arterial thrombi (7.5%), venous thrombi (7.5%), and nephritis (52.5%). The serological tests of SLE showed ANA was +ve in 85%, anti dsDNA

72.5%, anti Sm in 45%, ACL IgG in 17.5%, ACL IgM in 2.5%, and anti B1

GP1 antibodies was present in 22.5% of patients. There were significant - ve relationship between anti B2GP1 antibodies and Raynoud's phenomenon, a significant highly positive relationship between anti B2 GP1 and cerebral lu- pus, repeated abortions and arterial thrombosis. Also there was a significant relationship between anti B2 GP1 and ACL IgG. The main clinical manifestations in 20 Egyptian patients with antiphospho- lipid syndrome showed venous thrombosis in 65%, arterial thrombosis in

40% and repeated abortion in 22.2% ACL IgG was present in 100% while

ACL IgM in 5% and anti B2 GP1 antibodies were present in 45% of the pa-Downloaded from https://academic.oup.com/rheumatology/article/42/suppl_1/79/1773205 by guest on 16 July 2023

Poster Session 2. Genetics: Non-HLA genes81

tients. There was a significant relationship between the presence of antiB2 GP1 and each of, occurrence of thrombocytopenia and mean age of patients. Conclusions:We concluded that anti B2 GP 1 is aq significant serological marker in SLE, APS and it was more associated with more clinical manifes- tations in SLE than APS.

Genetics: Non-HLA genes

194.POLYMORPHISM SCREENING OF THE T LYMPHOCYTE SPECIFIC

GLUCOCORTICOID RECEPTOR PROMOTER

A Stevens

1,2 ,DRay 1 , R Donn 2 1

Endocrine Sciences Research Group,

University of Manchester, Manchester, United Kingdom; 2

ARC/EU,

University of Manchester, Manchester, United Kingdom Background:Glucocorticoids (Gc) are the most potent anti-inflammatory agents known, and are important for the treatment of multiple inflammatory conditions, including rheumatoid arthritis. However, their use is limited by side effects such as hypertension and osteoporosis. Population based vari- ation in response to Gc therapy has been described, but the genetic basis underlying this response has yet to be determined. The glucocorticoid recep- tor (GR) gene is a principle candidate for investigation of such variable Gc response. A polymorphism at codon 363 of GR is known to be associated with minimal changes in Gc sensitivity (1). Expression of the GR is deter- mined by multiple tissue specific promoters. Recently, Breslin et al described a T lymphocyte specific promoter/enhancer, 31Kb upstream of the GR cod- ing region, which, uniquely, is upregulated by Gc (2). As T cells are critical regulators of the immune response, and are key targets for Gc immuno- suppression, nucleotide variation within this region may significantly influ- ence the sensitivity of T lymphocytes to Gc, and as such be important in determining an individual's response to Gc therapy. Aim:To determine if the T lymhocyte-specific GR promoter contains poly- morphims which may influence Gc response.

Methods:Polymor-

phism screening was performed using dHPLC (Wave,Transgenomic) in 36 unrelated UK caucasians. Overlapping PCR fragments were generated to cover the entire 2028bp of the lymphocyte-specific GR promoter. Each fragment was<700bp so allow- ing a 99% sensitivity for heteroduplex detection. The entire 2028bp region was also sequenced (BigDye ddNTP) for 20 of the individuals studied. Results:No nucleotide variation was found across the lymphocyte specific GR promoter in any of the 36 UK caucasian individuals investigated. Conclusions:No genetic variation was seen in the UK caucasian sample set studied. Single nucleotide polymophism (SNP) frequency varies through- out the genome, but on average a SNP is thought to occur every 1Kb (3). If any nucleotide changes do exist within the T lymphocyte specific promoter of the GR they will be present at a frequency of<2.7%, so limiting their potential informativeness in genetic studies of Gc response.

References

[1] Huizenga et al. (1998) J Clin Endocrinol Metab. 83(1);144-151 [2] Breslin et al. (2001) Mol Endocrinol. 15;1381-1395. [3] Miller & Kwok (2001) Hum Mol Genet. 10(20) 2195-2198.

195.NON-HLA GENETIC INFLUENCES ON OUTCOME OF

INFLAMMATORY POLYARTHRITIS: PILOT DATA USING PRESENCE OF

EROSIONS BY 5 YEARS AS THE OUTCOME MEASURE

ABarton

1 ,HPlatt 3 ,FSalway 3 , E Barrett 2 , D Symmons 1 , S John 3

A Silman

1 1 ARC-EU, University of Manchester, Manchester, United

Kingdom;

2 Norfolk Arthritis Register, Norfolk and Norwich University

Hospital, Norfolk, United Kingdom;

3

Centre for Intergrated Genomic

Medicine, University of Manchester, Manchester, United Kingdom Background:A major goal in the management of inflammatory arthritis (IP) is to identify, at presentation, patients who will develop more severe disease in order to target aggressive therapies appropriately. Previous studies have reported associations of the TNFαand CCR5 genes with erosive outcome in hospital recruited patients with rheumatoid arthritis but, in order to separate susceptibility from severity factors, ideally the study group should comprise an inception cohort of patients with early IP followed prospectively. Aim:To investigate genetic determinants of presence, extent or progression of erosive change by 5 years in IP patients recruited from the Norfolk Arthritis Register.Methods:DNA was available for 438 patients with IP (swelling of 2 or more joints for>4weeks) all of whom were recruited within 6 months of symp- tom onset. Hand and feet radiographs (scored by the Larsen method) were available for all patients at 5 years and for 66% patients at 1 year. Single nucleotide polymorphisms (SNPs) in the TNFαgene were genotyped using a primer extension technique (SNaPshot, ABI). A 32bp deletion in the CCR5 gene was genotyped by size. As disease modifying treatment may mask the influence of genetic determinants of outcome, this was adjusted for in the analysis. Results:No association was detected with any of the polymorphisms tested with either presence of erosions nor the extent (Larsen score) (Table1) either at 1 or 5 years or with progression of change. Larsen score by TNFαallele and carriage of 32 bp CCR5 deletion. OR (95%CI) Allele Non-erosive Larsen less than Larsen greater than (n=244) median (n=101) median (n=93)

32bp CCR5 deletion 1.0 1.3(0.8-2.3) 0.6(0.8-1.2)

TNFαalleles:

-1031-T -1031-C 1.0 1.2(0.7-2.0) 1.5(0.9-2.6) -863-C -863-A 1.0 1.3(0.7-2.4) 1.7(0.9-3) -857-C -857-T 1.0 1.0(0.5-2.1) 0.7(0.3-1.5) -376-G -376-A 1.0 2.1(0.5-9.0) 2.3(0.5-9.8) -308-G 1.0 1.5(0.8-2.7) 1.5(0.8-2.8) -308-A -238-G -238-A 1.0 0.9(0.4-2.6) 1.5(0.6-3.6) +489-G
+489-A 1.0 1.2(0.6-2.4) 0.8(0.4-1.8)
+851-A
+851-G 1.0 1.3(0.5-3.1) 1.1(0.4-2.8)
+1304-A 1.0 1.0(0.5-2.2) 1.1(0.5-2.5)
+1304-G

OR = odds ratio, CI = conÞdence interval

Conclusions:We have not demonstrated a role of these genes with the de- velopment of erosions. Further modelling combining other genetic with clin- ical and environmental factors may improve the ability to identify individuals at high risk of this outcome. Genotyping at the CCR5 locus was funded by Astra Zeneca Pharmaceuti- cals Ltd.

196.TRANSFORMING GROWTH FACTOR BETA-1 GENE

POLYMORPHISMS AND ANKYLOSING SPONDYLITIS

E Jaakkola

1 , I Herzberg-Wallbank 1 ,A-MSims 1 , L Bradbury 1 , A Calin 2

K Laiho

3 , A Cranequotesdbs_dbs19.pdfusesText_25