Polymorphism of HLA-DMA and DMB alleles in patients with systemic lupus erythematosus

OBJECTIVE: To evaluate the contribution of HLA-DM alleles to susceptibility to systemic lupus erythematosus (SLE) in a Caucasian population. METHODS: HLA-DMA and DMB alleles were studied in 73 patients with SLE, 147 randomly selected controls, and 86 HLA-DRB1 genotype matched controls by oligotyping of polymerase chain reaction amplified genomic DNA with sequence-specific oligonucleotide probes. RESULTS: There was a significant presence of HLA-DMA*0103, DMA*0104, and DMB*0102 in the SLE patients compared with the randomly selected controls. After stratification of patients and matched controls according to DRB1 genotypes, only HLA-DMA*0104 was increased in SLE patients negative for the SLE susceptibility HLA-DR alleles. For the patients and controls positive for HLA-DR allele-susceptibility for SLE, HLA-DMA*0103, DMA*0104, DMB*0102, and DMB*0103 alleles tended to be more frequent, but without reaching statistical significance. No correlation was found between HLA-DM phenotype frequencies and any clinical or biological manifestations of SLE. CONCLUSION: This is the first study evaluating the influence of HLA-DM in a Caucasian SLE population. Our results suggest that HLA-DMA*0104 may represent a novel allele of susceptibility to SLE.     

Measles in bone marrow transplant recipients during an outbreak in S?o Paulo, Brazil.

In 1997, a measles outbreak was identified in S?o Paulo. Between February and December, 20 185 cases were confirmed. From April to July 1997, a seroepidemiologic survey was conducted to identify the recipients of bone marrow (BM) transplants who were susceptible to measles and the occurrence of measles in this population. A total of 156 patients were screened by enzyme immunoassay (EIA). Patients with IgG titers more than 100 mIU/mL were considered immune. Measles reimmunization records were also reviewed. Thirty-two vaccinated patients underwent serologic evaluation. Six of 22 patients (27.3%) within 3 years after vaccination lost measles immunity, in contrast to 7 of 10 patients (70%) vaccinated longer than 3 years previously (P =.049). Among the 122 nonvaccinated patients, 41 (33.6%) were susceptible to measles: 4 of 47 patients (8.5%) within the first year after BM transplantation (BMT), and 37 of the 75 patients (49.3%) after the first year after BMT (P <.001). Eight recipients acquired measles, confirmed by serology (EIA). High-avidity IgG antibodies were observed in the acute phase of measles, suggesting a secondary immune response. Measles interstitial pneumonia was observed in one patient. Seven patients had mild symptoms. Exanthema was present in all patients. All but one patient had fever and nonproductive cough. Koplik spots could be observed in 5 patients. Measles can be mild in BM transplant recipients. Exanthema is frequently present but not often typical. Immunity to measles decreases after day +365 after BMT. Additional studies are needed to evaluate the safety of measles vaccine after the first year of BMT, mostly during outbreaks.     

Chikungunya,Dengue, and Zika in Immunocompromised Hosts

Purpose of Review

Describe the characteristics of chikungunya, dengue, and Zika in transplant recipients and immunocompromised hosts.

Recent Findings

Stem cell/bone marrow grafts, organs, and blood transfusions can transmit CHIKV/DENV/ZIKV infections, which are clinically similar, resembling influenza-like illness. Laboratory confirmation is necessary. In the acute phase, RT-PCR is preferred. DENV and ZIKV serology may cross-react. Delayed engraftment and extended viruria is observed in ZIKV+/HSCT recipients, while longer viremia is observed in DENV+/HSCT patients. Arbovirus persistence in organ tissues is generally unknown. Vaccine development is in early stages for CHIKV/ZIKV. No data is available to recommend the licensed DENV vaccine in transplant recipients.

Summary

In endemic areas, the assessment of epidemiological risk is mandatory. Donor deferral for 120 days in suspected or confirmed ZIKV+ has been recommended, while CHIKV+ donors should wait 30 days. No deferral is recommended for DENV+ donors. CHIKV/DENV/ZIKV tests should be included in the differential of febrile neutropenia and other transplant syndromes. Reassessment of DENV serology is urgently needed. Prospective studies are necessary to determine the impact of CHIKV/DENV/ZIKV in this special population.

     

Spoligotypes of Mycobacterium tuberculosis complex isolates from patients residents of 11 states of Brazil

One of the high tuberculosis (TB) incidence countries in the world, Brazil is characterized by considerable differences in TB incidence on regional and state level. In the present study, we describe Brazilian spoligotypes of 1991 Mycobacterium tuberculosis complex (MTC) clinical isolates from patients residents of 11 states from different regions of the country, diagnosed between 1996 and 2005. By performing spoligotyping on a large number of M. tuberculosis clinical isolates, one of the main objectives of this study was to determine the major genotype families causing TB in Brazil and to verify the region-associated genotype distribution. We observed a total of 577 distinct spoligopatterns, 12.6% of these corresponded to orphan patterns while 87.4% belonged to 326 shared-types (SITs). Among the latter, 86 SITs (isolated from 178 patients) had been observed for the first time in this study, the most frequent being SIT2517 which belonged to the T3-ETH lineage and was exclusively found among patients residents of Belém, the capital of the state of Pará (n=8 isolates). Irrespective of shared-type labeling, a total of 19.5% strains were unique (unclustered) in our study as opposed to 80.5% clustered isolates (189 clusters, size range from 2 to 205 isolates). The three largest clusters were SIT42 of the Latin-America & Mediterranean (LAM) 9 clade (10.3%), SIT53 of the T clade (7.6%), and SIT50 of the Haarlem clade (5.4%). The predominant MTC lineages in Brazil in decreasing order belonged to the LAM (46%); the ill-defined T (18.6%); the Haarlem (12.2%), the X (4.7%), the S (1.9%), and the East African Indian (EAI) (0.85%) families. The rest of clades grouped together as Mycobacterium africanum, Mycobacterium bovis, Beijing, Central Asian (CAS), and the Manu types, represented less than 1% of the strains. Finally, about 15% of the isolates showed spoligotype signatures that were not yet classified among well-defined lineages. In conclusion, we provide hereby a first insight into the population structure of MTC isolates in Brazil, showing the predominance of both LAM and T family and the existence of region-associated genotypes.     

Thyroid function testing evaluated on three immunoassay systems

Total thyroxine (TT₄), tracer uptake, thyroid-stimulating hormone (TSH), and free T₄ (FT₄) testing was examined in the ACS 180, Abbott IMx, and Stratus II systems. TSH sensitivity studies demonstrated that the ACS and IMx are second-generation assays; the Stratus showed between first- and second-generation performance. Except for one control below the detection limit, TSH imprecision was 3–10%. TSH accuracy was adequate for all systems. TT₄ imprecision was 4–7%, except for the lowest control with the Stratus (18%). TT₄ method agreement showed bias of about 20% between the systems. TT₄ accuracy was compromised at the low end for the Stratus II, but was satisfactory otherwise. FT₄ imprecision was 20% for the Stratus, <5% for the IMx and 6% for the ACS. Uptake assays showed imprecision of 5–10%. The laboratory diagnosis indicated by each system's FT₄ and calculated FT₄ Index results were compared to determine diagnostic accuracy. In routine specimens, different clinical classifications were observed for 25% of specimens with the ACS, 19% with the Stratus, and 7% with the IMx; in the altered protein group, the Stratus showed 9% discordant results, the ACS showed 3%, and the IMx 0%. Of the three systems examined here, the Abbott IMx system showed the best overall performance.©1995 wiley-Liss, inc.     

Treatment of soft cervical hernia by percutaneous intradiscal injection of aprotinin

Chemonucleolysis is widely used in the treatment of disease of the lumbar intervertebral disk. From a series of 34 patients the authors report their experience using this technique at the cervical level using aprotinin instead of chymopapain in cervical soft disk protrusion. They underline the technique, mechanism of aprotinin and indications.