Complementary DNA sequence of the HLA‐B*3924 allele1

We have isolated the complete coding region of HLA‐B*39 from a Spanish Caucasoid, using a new PCR primer for its 5′ untranslated region. The cDNA matched partial genomic sequences of B*3924, an allele whose distribution appears to be restricted to Mediterranean and Arabian Caucasoids. A single amino acid change exclusive to B*3924 (threonine‐98) distinguishes it from B*3903.     

Diagnostic utility of a multiplex herpesvirus PCR assay performed with cerebrospinal fluid from human immunodeficiency virus-infected patients with neurological disorders

We used a multiplex nested-PCR assay for the simultaneous detection in cerebrospinal fluid (CSF) of five human herpesviruses (HVs) (cytomegalovirus [CMV], Epstein-Barr virus [EBV], varicella-zoster virus [VZV], herpes simplex virus [HSV], and human herpesvirus 6 [HHV-6]) in a clinical evaluation of human immunodeficiency virus (HIV)-infected patients with neurological disorders. This method, which has the advantages of being rapid and economical, would be of particular interest for the diagnosis of neurological syndromes caused by more than one HV. We studied 251 CSF samples from 219 patients. HV DNA was demonstrated in 93 (37%) of the CSF samples (34% of the patients). CMV was the HV most frequently detected in our patients (25%), while EBV, VZV, HSV, and HHV-6 DNAs were present in significantly fewer cases (7, 4, 3, and 1%, respectively). When results were compared with the final etiological diagnoses of the patients, the multiplex HV PCR showed high specificity for the diagnosis of CMV and VZV neurological diseases and for cerebral lymphoma (0.95, 0.97, and 0.99, respectively). The sensitivity of the assay was high for CMV disease (0.87), was low for cerebral lymphoma (0.33), and was not evaluable for VZV disease due to the small number of patients with this diagnosis. Nevertheless, detection of VZV DNA had possible diagnostic value in four of the nine cases, and EBV DNA amplification always predicted the diagnosis of cerebral lymphoma in patients with cerebral masses. Detection of HSV DNA was frequently associated with CMV amplification and fatal encephalitis. HHV-6 was not considered to have a pathogenetic role in the three cases in which it was detected. This multiplex HV PCR assay is a specific and clinically useful method for the evaluation of HIV-infected patients with neurological disorders related to HV.     

Cathepsin C gene: First compound heterozygous patient with Papillon-Lefèvre syndrome and a novel symptomless mutation

Papillon-Lefèvre syndrome (PLS) has recently been shown to be caused by mutations in the cathepsin C gene resulting in periodontal disease and palmoplantar keratosis. Thirteen different homozygous mutations have been characterised in PLS patients of different ethnic origin. In the present paper, a PLS patient is described who carries two novel mutations (706G>T and 872G>A) in the paternal and maternal chromosomes, respectively. This is the first compound patient described so far. In addition, a novel symptomless mutation (458C>T) in the cathepsin C gene is described in three homozygous individuals. Thus, not all mutations should be considered as a cause of disease, whether case studies or general population screening is performed. Another already described mutation that provoked the Haim-Munk syndrome (HMS) in Indian Jews has also been found to give rise to PLS in a Spanish family from Madrid. On the other hand, PLS patients are ameliorated by retinoids, which indicates that retinoids may be used as therapeutic agents in this immune system deficiency.     

The novel HLA-Cw*1802 allele is associated with B*5703 in the Bubi population from Equatorial Guinea

The HLA-Cw*1801 specificity, a Cw7/Cw4 hybrid allele, has recently been described in association with B*8101 (formerly B"DT"). In this study, the new Cw*1802 variant, differing from Cw*1801 at exon 5. is found associated with B*5703 in Bubi individuals from Equatorial Guinea. Confirmatory complete coding regions of B*5703 and B*3910 are also reported.     

Evolution of MHC-G in humans and primates based on three new 3'UT polymorphisms

MHC-G is a class Ib (non-classical) major histocompatibility complex (MHC) whose functional and evolutionary characteristics are still under scrutiny. The study of noncoding sequences in the MHC genes may provide important phylogenetic information. In this work we have sequenced the MHC-G exon 8, which encodes for the 3'UT region, in different species of primates. It has been shown that: (1) a previously described 14 base pair (bp) deletion polymorphism is human-specific and the HLA-G alleles may be classified according to its absence or presence; (2) another newly described 3 bp deletion/insertion polymorphism is also human-specific; and (3) another newly described 51 bp deletion polymorphism is common to Pongidae and humans, but is not found in other primates belonging to the Cercopithecinae family. A hypothesis on the evolutionary pathway of this gene is put forward in the light of these findings.     

Activity of aphids associated with lettuce and broccoli in Spain and their efficiency as vectors of Lettuce mosaic virus

This research sought to identify the aphid virus vector species associated with lettuce and broccoli crops in Spain, and to determine their population dynamics and ability to transmit Lettuce mosaic virus (LMV). Green tile traps and Moericke yellow water-pan traps were used to monitor aphid flights during the spring and autumn growing seasons of 2001. Aphid species feeding on lettuce were counted weekly. The transmission efficiencies of LMV were determined for the aphid species caught most frequently. The Moericke traps generally caught more aphid species than the tile trap, but the latter was the most suitable to estimate flight activity of species involved in virus spread. Spring aphid catches indicated that the main aphid species landing on lettuce in the regions of Madrid and Murcia was Hyperomyzus lactucae, but Brachycaudus helichrysi was also abundant in both regions. In broccoli in the Navarra region, the most abundant species in spring were Aphis fabae, B. helichrysi and H. lactucae. In autumn-sown crops, the main species landing on lettuce in the Madrid region were Hyadaphis coriandri and Aphis spiraecola. In Murcia, A. spiraecola and Myzus persicae were the most abundant, while in Navarra, Therioaphis trifolii, and various Aphis spp. were the most numerous landing on broccoli. The main aphid species colonising lettuce was Nasonovia ribisnigri, but other less abundant colonising species were Aulacorthum solani and Macrosiphum euphorbiae. The most efficient vectors of LMV were M. persicae, Aphis gossypii and M. euphorbiae, while A. fabae and H. lactucae transmitted with low efficiency, and Rhopalosiphum padi and N. ribisnigri did not transmit. Occurrence of LMV epidemics in central Spain in relation to aphid flights and the role of weeds as virus reservoirs is discussed.     

Expansion and clonal deletion of peripheral T cells induced by bacterial superantigen is independent of the interleukin-2 pathway

Injection of the bacterial superantigen Staphylococcus aureus enterotoxin B (SEB) into mice provokes a rapid expansion and subsequent contraction of the pool of SEB-reactive T cells bearing T cell receptor (TcR) V_β8 gene products. Given that interleukin 2 (IL-2) stimulates proliferation, abolishes anergy, and counteracts apoptotic cell death in T cells in vitro, we tested whether the IL-2 synthesis inhibitor cyclosporin A (CsA) or a vaccinia virus recombinant releasing high amounts of human IL-2 modulate SEB responses in vivo. Surprisingly, neither IL-2 nor CsA were able to change the in vivo kinetics and magnitude of SEB-induced expansion, unresponsiveness to SEB, and peripheral clonal deletion of T cells expressing products of the SEB-reactive TcR V_β8 gene family. In accord with these in vivo observations, IL-2 is incapable of reversing “anergy” and apoptotic cell death of V_β8⁺ SEB-reactive T cells isolated from SEB-primed mice in vitro. Accordingly, upon SEB injection V_β8⁺ T cells expand rapidly, without expressing IL-2 receptor (IL-2R)α chains in vivo, although SEB induces IL-2R α in vitro. Altogether, these results indicate that the IL-2/IL-2R-mediated pathway is not involved in T cell repertoire modulation by bacterial superantigens. Moreover, the data suggest that unresponsiveness of V_β8⁺ T cells from SEB-primed mice is not a reversible process, but involves an unreversible commitment to programmed cell death. Absence or presence of IL-2 responsiveness could be a hallmark to distinguish truly reversible anergy and peripheral clonal deletion.