Oral myeloid cells uptake allergoids coupled to mannan driving Th1/Treg responses upon sublingual delivery in mice.

BACKGROUND: Polymerized allergoids coupled to nonoxidized mannan (PM-allergoids) may represent novel vaccines targeting dendritic cells (DCs). PM-allergoids are better captured by DCs than native allergens and favor Th1/Treg cell responses upon subcutaneous injection. Herein we have studied in mice the in vivo immunogenicity of PM-allergoids administered sublingually in comparison with native allergens. METHODS: Three immunization protocols (4-8 weeks long) were used in Balb/c mice. Serum antibody levels were tested by ELISA. Cell responses (proliferation, cytokines, and Tregs) were assayed by flow cytometry in spleen and lymph nodes (LNs). Allergen uptake was measured by flow cytometry in myeloid sublingual cells. RESULTS: A quick antibody response and higher IgG2a/IgE ratio were observed with PM-allergoids. Moreover, stronger specific proliferative responses were seen in both submandibular LNs and spleen cells assayed in vitro. This was accompanied by a higher IFNγ/IL-4 ratio with a quick IL-10 production by submandibular LN cells. An increase in CD4+ CD25high FOXP3+ Treg cells was detected in LNs and spleen of mice treated with PM-allergoids. These allergoids were better captured than native allergens by antigen-presenting (CD45+ MHC-II+ ) cells obtained from the sublingual mucosa, including DCs (CD11b+ ) and macrophages (CD64+ ). Importantly, all the differential effects induced by PM-allergoids were abolished when using oxidized instead of nonoxidized PM-allergoids. CONCLUSION: Our results demonstrate for the first time that PM-allergoids administered through the sublingual route promote the generation of Th1 and FOXP3+ Treg cells in a greater extent than native allergens by mechanisms that might well involve their better uptake by oral antigen-presenting cells.

Factors associated with hyperhomocysteinaemia in Mexican patients with rheumatoid arthritis.

BACKGROUND: Hyperhomocysteinaemia is a factor related to the development of atherosclerosis in rheumatoid arthritis (RA). However, Hispanics with RA develop high rates of coronary disease; there are no studies about the frequency and factors related to high levels of homocysteine in Mexican patients. OBJECTIVE: To evaluate the prevalence and characteristics associated with hyperhomocysteinaemia in Mexican patients with RA. METHODS: One hundred and fifty-two patients with RA were compared with 153 controls. The assessment in RA included clinical characteristics, disease activity (RADAR), functioning (HAQ-Di and global functional status), comorbidity, and radiological damage. Laboratory determinations included total serum homocysteine (tHcy), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), and lipid profile. RESULTS: Median levels of homocysteine were higher in RA compared with controls (11.3 vs. 9.3, p<0.001). Twenty per cent of the patients with RA had hyperhomocysteinaemia (>15 micromol/L) compared with 6% in controls (p<0.001). There was statistical association between hyperhomocysteinaemia in RA with male gender (p<0.001), impairment in the global functional status (p = 0.004), higher radiological damage (p = 0.001), and CRP (p = 0.04). There was no association with RADAR, HAQ-Di, or RF, methotrexate dose or duration of use. In the adjusted multivariate model, the two variables associated with higher risk for hyperhomocysteinaemia were male gender (OR = 4.2, 95% CI 2 to 12, p = 0.006) and higher radiological damage (III-IV) (OR = 3.4, 95% CI 1.3 to 9, p = 0.01). CONCLUSIONS: Our data show a high prevalence of hyperhomocysteinaemia in Mexican patients with RA. More effort is required to evaluate and treat earlier this coronary risk factor.

Serum concentrations of aminoterminal propeptide of type III procollagen and propeptide of human type I procollagen in systemic lupus erythematosus.

The purpose of this study was to assess the association between the serum levels of aminoterminal propeptide of type III procollagen (PIIINP) and carboxyterminal propeptide of type I procollagen (PICP) with disease activity and damage in systemic lupus erythematosus (SLE). Thirty-three patients with SLE were compared with 31 controls. The assessment in SLE included disease activity indices (SLEDAI, MEX-SLEDAI) and damage index (SLICC/ACR). PIIINP and PICP were measured by radioimmunoassay. Compared with controls, mean levels of PIIINP were higher in SLE (2.9+/-1.8 vs. 1.8+/-1.2, P=0.006). PICP was also increased in SLE versus controls (163+/-94 vs. 102+/-62, P=0.007). PIIINP was correlated with SLICC/ACR (r=0.33, P=0.048). No correlation was observed between PICP and PIIINP with other clinical or therapeutic variables. These preliminary data suggests a role of PIIINP as a marker for chronic damage. Follow-up studies are required to evaluate its utility in predicting future damage.

[Patterns of health care in an out patient rheumatologic clinic]. / La atención médica en reumatología en un hospital de segundo nivel de atención.

INTRODUCTION: Studies evaluating the pattern of diseases evaluated by rheumatology services are required to improve the planning of healthcare resource distribution. AIM: To describe the pattern of diseases motivating consultations in an outpatient clinic of a secondary care center in Guadalajara, Mexico. MATERIAL AND METHODS: A cross-sectional, descriptive study was performed. Data on the diseases evaluated in the rheumatology service and other healthcare indicators were obtained through a search of the hospital's computerized database. The number of initial and repeat consultations, their distribution by age and sex, the mean monthly number of prescriptions, and other indicators of performance were identified. RESULTS: There were 5,790 consultations in 1 year (26% were initial visits). The three most frequent diseases were: rheumatoid arthritis (47.1%, 95% CI 46-48%), systemic lupus erythematosus (12.7%, 95% CI 12-14%), and ankylosing spondylitis (7.7%, 95% CI 7-8%). Four women were attended for each man. Consultations were most frequent in the group aged 30-59 years old. The mean number of consultations per rheumatologist/month was 242, with a mean of 2.5 prescriptions per patient. The rate of compliance with appointments was 85%. A mean of 7.5 were diagnosed with temporary work disability for each rheumatologist/month. CONCLUSIONS: The most prevalent disorders in our outpatient rheumatology clinic were inflammatory joint diseases and systemic autoimmune diseases. These disorders required a high proportion of health-care resource. Further studies are required to evaluate the costs of these resources with the aim of establising better strategies for the health care needs in these patients.