-463 G/A myeloperoxidase promoter polymorphism in giant cell arteritis.

OBJECTIVE: To investigate potential associations between-463 G/A myeloperoxidase (MPO) promoter polymorphism and susceptibility to, and clinical features of giant cell arteritis (GCA). METHODS: A total of 156 patients with biopsy-proven GCA who were residents of Reggio Emilia, Italy, and 235 population-based controls from the same geographic area were genotyped for-463 G/A promoter polymorphism of the MPO gene by molecular methods. The patients were subgrouped according to the presence or absence of polymyalgia rheumatica and severe ischaemic complications (visual loss and/or cerebrovascular accidents). RESULTS: The distribution of the MPO-G/A genotype differed significantly between patients with GCA and the controls (p(corr) = 0.003). Allele G was significantly more frequent in patients with GCA than in the controls (p(corr) = 0.0002, OR 2.0, 95% CI 1.4 to 2.9). Homozygosity for the G allele was significantly more frequent in patients with GCA than in controls (p(corr) = 0.0002, OR 2.2, 95% CI 1.4 to 3.4). No significant associations were found when patients with GCA with and without polymyalgia rheumatica or with and without severe ischaemic complications were compared. CONCLUSIONS: Our findings show that the-463 G/A promoter polymorphism of the MPO gene is associated with GCA susceptibility and support a role for MPO in the pathophysiology of GCA.

Absence of the association with CC chemokine receptor 5 polymorphism in polymyalgia rheumatica.

OBJECTIVE: Elevated RANTES serum levels are present in polymyalgia rheumatica (PMR) patients with active disease. Chemokines may contribute to the inflammatory PMR process through their binding to CC chemokine receptor 5 (CCR5). The aim of this study was to examine if the 32 base pair deletion allele in CCR5 (CCR5 delta 32 allele) might be associated with PMR susceptibility and influence the disease outcome. METHODS: We enrolled 88 consecutive patients with PMR residing in the Reggio Emilia area (Italy) who had a follow-up duration of at least one year. As a control group we used 86 healthy blood donors from the same geographic area. The CCR5 genotype of all PMR patients and controls was studied by polymerase chain reaction amplification of the region which includes the 32 deletion (CCR5 delta 32). RANTES serum levels were measured by commercial ELISA kits in CCR5 delta 32 heterozygous and CCR5 homozygous PMR patients at diagnosis before starting corticosteroid therapy and again after 6 months of therapy, as well as in 28 healthy subjects over 50 years of age. RESULTS: Frequencies of the CCR5 and CCR5 delta 32 alleles in patients and controls did not differ significantly. Homozygosity for CCR5 delta 32 was not detected in PMR patients and was detected in only one of the controls. No significant differences were observed between the patients carrying the CCR5 delta 32 allele and those homozygous for the normal CCR5 allele when we compared sex, presence of distal synovitis and systemic signs and/or symptoms, initial and cumulative prednisone dose, duration of therapy, ESR at diagnosis, frequency of relapse/recurrence and RANTES serum levels at diagnosis and after 6 months of corticosteroids. CONCLUSION: These results indicate that the frequency of the 32 deletion of the CCR5 receptor was not significantly different between PMR patients and healthy controls, and this genotype does not appear to be associated with the susceptibility to or severity of PMR.

Interleukin-1 cluster and tumor necrosis factor-alpha gene polymorphisms in polymyalgia rheumatica.

OBJECTIVE: To investigate whether polymorphisms in the interleukin (IL)-1 locus (human chrom. 2q13) and TNF-alpha gene are associated with susceptibility to or severity of polymyalgia rheumatica (PMR). METHODS: The study included 92 consecutive PMR patients diagnosed over a 5-year period who were prospectively followed-up for at least one year and 79 healthy controls over the age of 50 residing in the same area. All the patients and controls were Caucasians of Italian origin. We tested the allelic distribution of IL-1A (+4845), IL-B (-511), IL-B (+3954), IL-1RN Intron 2 VNTR and TNFA (-308). Frequencies were compared in the patient and control groups. RESULTS: A statistically significant association between PMR patients and the IL1RN*2 allele in the homozygous state was found [OR 8.46 (95% CI 1.05-68.31)]. The polymorphisms in the other genes of the IL-1 gene cluster did not reveal any association with PMR when compared with controls. A weak association between PMR patients and the TNF2 allele was also present [OR 2.09 (95% CI 1.0-4.17)]. None of the gene variants studied was associated with the disease severity of PMR. CONCLUSION: Our findings show that IL1RN*2 allele, particularly in the homozygous state, is associated with susceptibility to, but not with the severity of, PMR.

HLA-DRB1 alleles associated with rheumatoid arthritis in Northern Italy: correlation with disease severity.

The aim of the study was to evaluate the relationship between the presence of the 'rheumatoid epitope', defined by a sequence motif in the HLA-DRB1 alleles, rheumatoid factor and disease severity in Northern Italian patients with rheumatoid arthritis (RA). Twenty-nine DR4-positive and 57 DR4-negative RA patients were studied. Each DR4-positive patient was matched with two DR4-negative controls of similar disease duration and sex. HLA-DRB1 alleles were determined in the 86 patients and 351 controls from the same geographical area. The patients were retrospectively evaluated for extra-articular features (EAF) and radiographic damage. The rheumatoid epitope was expressed in 45% of patients. No significant differences in the presence of rheumatoid factor, EAF and articular damage were observed between patients with no, one or two doses of epitope. However, the patients encoding the epitope by an HLA-DR4 allele had a higher number of eroded joints and a higher Larsen score compared to those without the epitope. No differences were present between patients expressing HLA-DRB1*01 alleles and those lacking the rheumatoid epitope. Even in the absence of expression of the rheumatoid epitope, seropositive patients had more EAF and more erosive disease compared to those who were seronegative. Even if most Northern Italian RA patients do not express the rheumatoid epitope, the radiological severity of disease is associated with HLA-DRB1*04 alleles.

Low molecular weight IgM in primary Sjögren's syndrome.

Low molecular weight IgM (LMW IgM), the monomeric subunit of pentameric IgM, was measured in the serum of 27 patients with primary Sjögren's syndrome. LMW IgM was also measured in a control group consisting of 24 patients with psoriatic arthritis (PA) and 8 patients with active rheumatoid arthritis (RA). LMW IgM was found in the majority of patients with primary SS (63%) and those patients had a longer disease duration than those without SS (80.7 +/- 43.9 months vs 37 +/- 18.3, p = 0.01). Although the differences were not significant, SS patients with LMW IgM showed higher rates of: seropositive disease (71% vs 50%), anti-Ro (59% vs 30%) and anti-La antibodies (12% vs 0%), extraglandular involvement (76% vs 60%) and raised gammaglobulins levels (47% vs 30%) compared to those without LMW IgM. Our only two patients with active RA and vasculitis had LMW IgM. None of the patients with PA showed LMW IgM, regardless of their Kammer subgroup classification, disease activity or radiological evidence of erosions. The presence of LMW IgM in a high percentage of patients with primary SS appears to be the expression of a dysregulation of B cell state that may predispose these patients to developing malignant lymphoproliferation.

The role of interleukin 1, erythropoietin and red cell bound immunoglobulins in the anaemia of rheumatoid arthritis.

Since interleukin 1 (IL-1) and erythropoietin (Epo) are believed to play a role in the pathogenesis of rheumatoid arthritis (RA) anaemia we measured IL-1 alpha and Epo concentrations in 10 RA patients with chronic disease anaemia (CDA) and in 14 RA patients without anaemia. Anaemic RA patients had significantly higher IL-1 alpha concentrations than patients without anaemia. IL-1 alpha correlated negatively with haemoglobin and correlated positively with ESR. The results of a multivariate analysis showed that the best predictors of the presence and absence of anaemia were IL-1 alpha and ESR. No clinical parameters permitted a distinction between these two groups of patients. Epo levels were not different in anaemic and non-anaemic RA patients. No correlation was found between Hb and Epo, indicating the presence of an impaired Epo response in RA patients with CDA. We completed our study with the determination of the mean red cell lifespan and with the quantification of IgG and IgM bound to the surfaces of red blood cells (RBC-IgG and RBC-IgM) using a sensitive ELISA method. We observed a modest reduction in red cell survival in anaemic RA patients compared to normal controls. We did not find any correlation between Hb and red cell lifespan and between Hb and RBC-IgG. RBC-IgG and RBC-IgM were not found to be more elevated in anaemic RA than in non-anaemic patients.

Clinical subgroups and HLA antigens in Italian patients with psoriatic arthritis.

The frequencies of HLA antigens were studied in 101 Italian patients with psoriatic arthritis. The total group showed a significant increase in frequency of A1 and B38, and a reduction of B5 when compared to healthy controls. No association between DR and/or DQw antigens and PA were demonstrated. The comparisons between the clinical subgroups and normal controls revealed a significant association of B38 with asymmetric peripheral arthritis, B27 and B39 with spondylitis (with or without peripheral involvement). When intergroup comparison were made, the patients with spondylitis had an increase in frequency of B27 and DQw3 as compared to those with symmetric and asymmetric peripheral disease. DR4 and DRw53 were associated with earlier age of onset of arthritis. There were also significant associations between DQw3 and severe disease, and between A9, B5 and presence of erosions and joint space narrowing. No association with DR4 was showed in a subgroup of patients with symmetric polyarthritis without DIP involvement.

Bartter's syndrome and chondrocalcinosis: a possible role for hypomagnesemia in the deposition of calcium pyrophosphate dihydrate (CPPD) crystals.

A new case of association between Bartter's syndrome and chondrocalcinosis is reported. The patient was shown to have marked hypomagnesemia. Indomethacin and magnesium therapy was started and resulted in increased magnesemia, even if it did not reach normal levels. There was complete remission of articular symptoms and no progression on the radiological picture after 2 years of continuous magnesium and indomethacin therapy. The 7 available family members were studied to assess the possible presence of a familial form of chondrocalcinosis and/or hypomagnesemia. The literature is reviewed and reports of previously described associations between Bartter's syndrome and chondrocalcinosis are summarized. The possible role of hypomagnesemia in predisposing to deposition of calcium pyrophosphate dihydrate crystal in cartilagine is also discussed.

Polymyalgia rheumatica and giant cell arteritis: a 5-year epidemiologic and clinical study in Reggio Emilia, Italy.

Among the population of Reggio Emilia, Italy, 56 patients with polymyalgia rheumatica (PR) and giant cell arteritis (GCA) were identified during the 5-year period 1981-85. The average annual incidence rates of PR and GCA were 12.8 and 8.8 respectively per 100,000 population aged 50 years or older. Forty-nine patients were followed up and the mean duration of follow-up was 32 months. All the patients received steroid therapy. We have evaluated the cumulative probability of requiring continued steroid therapy between patients with PR only, GCA only, and PR associated with GCA using life-table methods with permanent discontinuation of therapy as an end point. The different duration of steroid therapy between these 3 groups did not achieve statistical significance by the method of Lee and Desu. We identified a 5 variable discriminant function that correctly predicted whether the duration of therapy would be longer or shorter than 16 months (median duration of therapy) in 80% of our patients followed up for at least 24 months. The presence of synovitis in PR is also discussed.

Clinical assessment of sulbenicillin in acute respiratory tract infection.

The effectiveness of sulbenicillin was assessed in the treatment of 15 adults, 12 suffering from bronchopneumonia and three from lobar pneumonia. Six patients had concomitant complications. At a parenteral dose of 2 g twice or thrice daily for at least seven days, all patients became afebrile by the sixth day, and chest X-rays became normal in nine patients and improved in five. It is concluded that sulbenicillin, which was well tolerated, is clinically effective in the treatment of severe respiratory tract infections, also in patients with major impairment of their immune response systems.