Motorcycling performance and sleepiness during an extended ride on a dynamic simulator: relationship with stress biomarkers.

OBJECTIVE: Powered two-wheelers (PTW) make up a large proportion of fatal accidents. The aim of this study was to investigate the effects of time-of-day and total sleep deprivation (SD) on simulated motorcycling performance during extended riding sessions (60 min), while evaluating stress mechanisms. APPROACH: A total of 16 healthy males participated in four simulated motorcycling sessions at 07:00, 11:00, 15:00 and 19:00, including city (8 min), country (2 min) and highway pathways (40 min), after a normal night of sleep and after total SD (30 h), in a randomized counterbalanced order. The recorded motorcycle parameters included: variation of lateral position, number of inappropriate line crossings (ILC), falls, riding errors, speed and speed limit violations. Subject parameters included the number of microsleeps in each pathway, the number of lapses during the 3-min psychomotor vigilance task (PVT-Brief version), and the Karolinska sleepiness scale (KSS) score. Saliva samples were used to assess cortisol (sC), α-amylase (sAA), and chromogranin-A (sCgA). ANOVAs and Pearson's correlation analysis were performed between these variables. MAIN RESULTS: Most parameters were influenced by an interaction effect between 'Motorcycling pathways' × 'SD' (speed (p < 0.05), legal speed violations (p < 0.01), variation of lateral position (p < 0.001), falls (p < 0.001), EEG-microsleeps (p < 005)). An interaction effect between 'SD' × 'Time-of-day' influenced the number of ILCs (p < 0.01), sC (p < 0.05) and sCgA (p < 0.05) levels. SD affected KSS scores (p < 0.001) and PVT lapses (p < 0.05). The highest disturbances were associated with highway motorcycling simulation. SIGNIFICANCE: Sleepiness due to circadian or SD and fatigue effects significantly affect riding and increase the risks involved with PTWs. The activation of both stress systems seems not sufficient to alleviate these deleterious effects.

[Visual outcomes four years after small incision lenticule extraction (SMILE) surgery on highly myopic eyes [French version]]. / La prédictibilité du SMILE sur quatre ans chez les myopes forts.

OBJECTIVE: To determine whether the visual outcomes of the refractive surgery technique, small incision lenticule extraction (SMILE), are stable, effective, and predictable for high myopia over a four-year period. RESEARCH DESIGN: This is a retrospective study. The data were collected between March 2012 and July 2016. PARTICIPANTS: Two hundred and forty-eight patients participated in the study; that is, 496 eyes: 140 eyes of 70 patients (52 women/18 men) were classified in the highly myopic group (refraction measured in spherical equivalent [RMSE]>-6D), and 356 eyes of 178 patients (98 women/80 men) in the control group (RMSE≤-6D). Follow-up tests were conducted immediately post-operatively (D+1), after three months, after one year, and after four years. Refraction, uncorrected visual acuity (UCVA), and best visual corrected acuity (BCVA) were measured. The highly myopic group (HMG) contained more women, and astigmatism was higher for this group than for the control group (CG). PRIMARY AND SECONDARY STUDY CRITERIA: These are BCVA, refractive stability, the index of safety (SI: BCVA preoperatively D+1/BCVA postoperatively), and predictability (the percentage of eyes within±0.5 D of the target). RESULTS: In both groups, UCVA was better after the fourth year than it was immediately after the procedure (HMG: P=0.001; CG: P=0.001). Although it differed at one year (P=0.01), the groups' refractive stability tended to converge over four years (P=0.138). Both groups' SI was identical in the four follow-up tests (P=0.734 at D+1; P=0.07 at M+1; P=0.160 at M3 and Y1; and P=0.274 at Y4). For the HMG, SI stability was attained after three months (1.00±0.1); whereas it was attained after one month (0.91±0.11) for the CG. Four years after the surgery, we observed that 87 % of the operated eyes in the HMG were within 0.5 D of the target. CONCLUSION: SMILE is a good refractive surgery technique for treating high myopia. It yields stable, safe, effective, and predictable results over four years.

Predictability of SMILE over four years in high myopes.

OBJECTIVE: To determine whether the visual outcomes of the refractive surgery technique small incision lenticule extraction (SMILE), are stable, effective, and predictable for high myopia over a four-year period. RESEARCH DESIGN: This is a retrospective study. The data were collected between March 2012 and July 2016. PARTICIPANTS: Two hundred and forty-eight patients participated in the study; that is, 496 eyes: 140 eyes of 70 patients (52 women/18 men) were classified into the highly myopic group (refraction measured in spherical equivalent (RMSE)>-6 D), and 356 eyes of 178 patients (98 women/80 men) into the control group (RMSE<-6 D). Follow-up tests were conducted immediately following the procedure (D+1), after three months, after one year, and after four years. Refraction, uncorrected visual acuity (UCVA), and best visual corrected acuity (BCVA) were measured. The highly myopic group (HMG) contained more women, and astigmatism was higher for this group than for the control group (CG). PRIMARY AND SECONDARY STUDY CRITERIA: These were BCVA, refractive stability, the index of safety (SI: BCVA preoperatively D+1/BCVA postoperatively), and predictability (the percentage of eyes within±0.5 D of the target). RESULTS: In both groups, UCVA was better after the fourth year than it was immediately after the procedure (HMG: P=0.001; CG: P=0.001). Although it differed at one year (P=0.01), the groups' refractive stability tended to converge over four years (P=0.138). The groups' SI was found to be identical in the four follow-up tests (P=0.734 at D+1; P=0.07 at M+1; P=0.160 at M3 and Y1; and P=0.274 at Y4). For the HMG, SI stability was attained after three months (1.00±0.1); whereas it was attained after one month (0.91±0.11) for the CG. Four years after the surgery, we observed that 87% of the operated-upon eyes in the HMG were within 0.5 D of the target. CONCLUSION: SMILE is a good refractive surgery technique for treating high myopia. It yields stable, safe, effective, and predictable results over four years.

In-flight automatic detection of vigilance states using a single EEG channel.

Sleepiness and fatigue can reach particularly high levels during long-haul overnight flights. Under these conditions, voluntary or even involuntary sleep periods may occur, increasing the risk of accidents. The aim of this study was to assess the performance of an in-flight automatic detection system of low-vigilance states using a single electroencephalogram channel. Fourteen healthy pilots voluntarily wore a miniaturized brain electrical activity recording device during long-haul flights ( 10 ±2.0 h, Atlantic 2 and Falcon 50 M, French naval aviation). No subject was disturbed by the equipment. Seven pilots experienced at least a period of voluntary ( 26.8 ±8.0 min, n = 4) or involuntary sleep (N1 sleep stage, 26.6 ±18.7 s, n = 7) during the flight. Automatic classification (wake/sleep) by the algorithm was made for 10-s epochs (O1-M2 or C3-M2 channel), based on comparison of means to detect changes in α, ß, and θ relative power, or ratio [( α+θ)/ß], or fuzzy logic fusion (α, ß). Pertinence and prognostic of the algorithm were determined using epoch-by-epoch comparison with visual-scoring (two blinded readers, AASM rules). The best concordance between automatic detection and visual-scoring was observed within the O1-M2 channel, using the ratio [( α+θ )/ß] ( 98.3 ±4.1% of good detection, K = 0.94 ±0.07, with a 0.04 ±0.04 false positive rate and a 0.87 ±0.10 true positive rate). Our results confirm the efficiency of a miniaturized single electroencephalographic channel recording device, associated with an automatic detection algorithm, in order to detect low-vigilance states during real flights.

Effect of one night of sleep loss on changes in tumor necrosis factor alpha (TNF-α) levels in healthy men.

Total sleep deprivation in humans is associated with increased daytime sleepiness, decreased performance, elevations in inflammatory cytokines, and hormonal/metabolic disturbances. To assess the effects of 40 h of total sleep deprivation (TSD) under constant and well controlled conditions, on plasma levels of TNF-α and its receptor (TNFR1), interleukin-6 (IL-6), cortisol and C-reactive protein (CRP), sleepiness and performance, 12 healthy men (29±3 years) participated in a 5-days sleep deprivation experiment (two control nights followed by a night of sleep loss and one recovery night). Between 0800 and 2300 (i.e. between 25 and 40 h of sleep deprivation), a serial of blood sampling, multiple sleep latency, subjective levels of sleepiness and reaction time tests were completed before (day 2: D2) and after (day 4: D4) one night of sleep loss. We showed that an acute sleep deprivation (i.e. after 34 and 37 h of sleep deprivation) induced a significant increase in TNF-α (P<0.01), but there were no significant changes in TNFR1, IL-6, cortisol and CRP. In conclusion, our study in which constant and controlled experimental conditions were realized with healthy subjects and in absence of psychological or physical stressors, an acute total sleep deprivation (from 34 h) was sufficient to induce secretion of pro-inflammatory cytokine such as TNF-α, a marker more described in chronic sleep restriction or deprivation and as mediators of excessive sleepiness in humans in pathological conditions.

Clinical and diagnostic approach in unsolved CDG patients with a type 2 transferrin pattern.

Dysmorphic features, multisystem disease, and central nervous system involvement are common symptoms in congenital disorders of glycosylation, including several recently discovered Golgi-related glycosylation defects. In search for discriminative features, we assessed eleven children suspected with a Golgi-related inborn error of glycosylation. We evaluated all genetically unsolved patients, diagnosed with a type 2 transferrin isofocusing pattern in the period of 1999-2009. By combining biochemical results with characteristic clinical symptoms, we used a diagnostic flow chart to approach the underlying defect in patients with congenital disorders of glycosylation-IIx. According to specific symptoms and laboratory results, we initiated additional, targeted biochemical and genetic studies. We found a distinctive spectrum of congenital disorders of glycosylation type 2-associated anomalies including sudden hearing loss, brain malformations, wrinkled skin, and epilepsy in combination with skeletal dysplasia, dilated cardiomyopathy, sudden cardiac arrest, abnormal copper and iron metabolism, and endocrine abnormalities in our patients. One patient with severe cortical malformations and mild skin abnormalities was diagnosed with a known genetic syndrome, due to an ATP6V0A2 defect. Here, we present unique congenital disorders of glycosylation type 2-associated anomalies, including both ATPase-related and unrelated cutis laxa and sensorineural hearing loss, a recently recognized symptom of congenital disorders of glycosylation. Based on our findings, we recommend clinicians to consider congenital disorders of glycosylation in patients with cardiac rhythm disorders, spondylodysplasia and biochemical abnormalities of the copper and iron metabolism even in absence of intellectual disability.

Clinical features, lectin staining, and a novel GNE frameshift mutation in hereditary inclusion body myopathy.

We present a comprehensive report of two siblings with hereditary inclusion body myopathy (HIBM). The clinical features and histological characteristics of the muscle biopsies showed the typical pattern of predominantly distal vacuolar myopathy with quadriceps sparing. This was confirmed by muscle MRI. PNA lectin staining showed an increased signal at the sarcolemma in patient muscle sections compared to control muscle, indicating reduced sialylation of glycoconjugates. Mutation analysis revealed compound heterozygous mutations in the GNE gene, encoding the key enzyme in sialic acid synthesis UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase: a missense mutation (c.2086G > A; p.V696M) previously described in HIBM patients of Indian origin, and a novel frame shift mutation (c.1295delA; p.K432RfsX17) leading to a premature stopcodon. These findings confirmed the diagnosis of HIBM on the histological, molecular and biochemical level.

Ophthalmological abnormalities in children with congenital disorders of glycosylation type I.

BACKGROUND: Children with congenital disorders of glycosylation (CDG) type Ia frequently present with ocular involvement and visual loss. Little is known, however, about the occurrence of ophthalmological abnormalities in other subtypes of CDG syndrome. METHODS: We evaluated 45 children sequentially diagnosed with CDG type I for the presence of ocular abnormalities at the time of the diagnosis and during follow-up. We compared the various ophthalmic findings in the different CDG subgroups. RESULTS: Of the 45 patients, 22 had CDG type Ia, nine had CDG type Ic and 14 had a so-far undiagnosed biochemical background (CDG type Ix). We found ocular anomalies in 28 of the 45 children. Three had unique findings, including congenital cataract, retinal coloboma and glaucoma. A few CDG type Ia patients showed a sequential occurrence of symptoms, including retinitis pigmentosa or cataract. CONCLUSIONS: Ophthalmic findings are frequent in CDG syndrome involving both the anterior and posterior segment of the eye. The disorder might lead to abnormal development of the lens or the retina, cause diminished vision, alter ocular motility and intraocular pressure. We suggest routine screening and follow-up for ophthalmological anomalies in all children diagnosed with CDG syndrome to provide early treatment and adequate counselling.

Congenital disorder of glycosylation type Ix: review of clinical spectrum and diagnostic steps.

Congenital disorder of glycosylation type I (CDG I) represent a rapidly growing group of inherited multisystem disorders with 13 genetically established subtypes (CDG Ia to CDG Im), and a high number of biochemically unresolved cases (CDG Ix). Further diagnostic effort and prognosis counselling are very challenging in these children. In the current study, we reviewed the clinical records of 10 CDG Ix patients and compared the data with 13 CDG Ix patients published in the literature in search for specific symptoms to create clinical subgroups. The most frequent findings were rather nonspecific, including developmental delay and axial hypotonia. Several features were found that are uncommon in CDG syndrome, such as elevated creatine kinase or arthrogryposis. Distinct ophthalmological abnormalities were observed including optic nerve atrophy, cataract and glaucoma. Two subgroups could be established: one with a pure neurological presentation and the other with a neurological-multivisceral form. The first group had a significantly better prognosis. The unique presentation of microcephaly, seizures, ascites, hepatomegaly, nephrotic syndrome and severe developmental delay was observed in one child diagnosed with CDG Ik. Establishing clinical subgroups and increasing the number of patients within the subgroups may lead the way towards the genetic defect in children with a so far unsolved type of the congenital disorders of glycosylation. Raising awareness for less common, non-CDG specific clinical features such as congenital joint contractures, movement disorders or ophthalmological anomalies will encourage clinicians to think of CDG in its more unusual presentation. Clinical grouping also helps to determine the prognosis and provide better counselling for the families.

Killer inhibitory receptor (CD158b) modulates the lytic activity of tumor-specific T lymphocytes infiltrating renal cell carcinomas.

In this study, we showed that renal tumors contain substantial subsets of CD8(+) p58(+) T cells. From 1 of these tumors, T cells were amplified in mixed lymphocytes-tumor cell cultures and p58(+) T cells were selected immunologically. After expansion, phenotypic and functional features of p58(+) and p58(-) T cells were examined. The p58(+) T cells expressed p58.2 receptor and corresponded to CD3(+), CD8(+), T-cell receptor (TCR) alpha/beta(+) T cells that were CD56(+) and CD28(-). Functionally, p58(+) T cells showed a low level of lytic activity against autologous tumor cells that was dramatically and specifically increased by anti-p58.2 monoclonal antibody. On the other hand, p58(-) CD8(+) T cells did not lyse autologous tumor cells and had non-major histocompatibility complex-restricted cytotoxicity against K562 and Daudi cells. A p58(+) cytotoxic T lymphocyte (CTL) clone (4C7) with the same characteristics as the p58(+) T-cell line was derived. This CTL clone did not lyse autologous normal B cells but lysed several HLA-A1(+) renal tumor cell lines. Analysis of TCR repertoire diversity showed that the p58(+) T-cell line contained 3 TCR rearrangements, whereas the TCR repertoire of p58(-) T cells was polyclonal. Interestingly, TCR transcripts of p58(+) T cells and of CTL clone 4C7 were detected as prominent ex vivo in tumor cells but not in peripheral blood mononuclear cells, suggesting that these cells are antigen specific and amplified at the tumor site. (Blood. 2000;95:2883-2889)

Effect of tumor growth factor-beta on NK receptor expression by allostimulated CD8+ T lymphocytes.

We have examined the influence of the immunosuppressive cytokine TGF-beta on NK receptor expression by T lymphocytes upon allogeneic activation. Using the primary mixed lymphocyte reaction (MLR), our data show that allostimulation induced the expression of CD94/NKG2-A on alloactivated CD8+ T cells. This expression was increased in the presence of TGF-beta whereas IL-15 had no significant effect. The blockage of CD94 and NKG2-A resulted in increased lysis of targets by alloactivated cytotoxic T cells. This increase was dependent on the activation state of T cells. Using PCR, we also demonstrated that TGF-beta had no effect on the transcription of non-inhibitory NKG2 molecules. The present results show that allostimulation can induce CD94 and further point out the role of TGF-beta in the induction of the CD94/NKG2-A receptor on alloactivated T cells.

TCR analysis reveals significant repertoire selection during in vitro lymphocyte culture.

The in vitro stimulation of T lymphocytes is frequently used as a technique to expand specific cells present at low precursor frequency in vivo. However, cells analysed after such procedures may no longer reflect those originally present in vivo because of the variable efficiency of outgrowth of different T cell subpopulations. To systematically assess this and to complement functional assays, we have analysed the TCR repertoire using a new high resolution RT-PCR method to determine TCR beta chain CDR3 transcript length. In the ex vivo analysis of tumor infiltrating lymphocytes (TIL) of renal cell carcinoma and glioblastoma patients, we observed and quantified oligoclonally expanded populations of T cells that were very susceptible to repertoire modification upon subsequent in vitro culture with autologous tumor cells. This in vitro repertoire skewing occurred preferentially with TIL rather than peripheral blood lymphocytes and we noted that tumor cells rather than normal cells of the same tissue type were the most potent inducers of the effect. It was striking that this selection was sometimes negative: certain prominent T cell populations that were highly represented in vivo disappeared after in vitro re-stimulation. This suggests that the presentation of tumor associated antigens during culture may eliminate rather than enrich for in vivo primed T cells. It is clear that in vitro functional tests cannot adequately describe all T cells with tumor specificity. Approaches that allow the assessment of potentially antigen-reactive T cell populations ex vivo are thus an important advance in the global appraisal of anti-tumor T cell immune responses.

Quantitative analysis of T helper 1, T helper 2, and inflammatory cytokine expression in patients after allogeneic bone marrow transplantation: relationship with the occurrence of acute graft-versus-host disease.

BACKGROUND: To further delineate the cytokine involvement in human acute graft-versus-host disease (GVHD), we analyzed cytokine expression in peripheral blood mononuclear cells (PBMC) from patients who developed acute GVHD after allogeneic bone marrow transplantation and from those who did not. METHODS: We used a highly quantitative and sensitive polymerase chain reaction assay based on the coamplification of an internal standard, with the cDNA derived from the mRNA of interest. Results are expressed in copy numbers, after normalization to a fixed amount of actin, allowing comparison between different samples. After a myeloablative regimen, 22 patients with hematological diseases received an unmanipulated allograft from a matched sibling. They were subsequently submitted to prophylactic immunosuppression. We examined the transcription of genes encoding cytokines in PBMC and skin biopsies. We selected T helper 1 (interferon ([IFN]gamma, interleukin [IL]-2), T helper 2 (IL-4, IL-10), and inflammatory (IL-1, IL-6) cytokines. RESULTS: Four weeks after bone marrow transplantation, the bulk of the PBMC population exhibited an increased expression of IL-1 and IL-6, with no major difference between GVHD+ and GVHD- patients. In addition, although IL-2 expression was not detected, increased levels of IFNgamma mRNA were observed in allografted patients, with higher levels in GVHD+ patients. In skin biopsies sampled at the beginning of GVHD, although low expression of IL-1 and IL-6 could be observed, neither type 1 (IL-2, IFNgamma) nor type 2 (IL-4, IL-10) cytokines could be detected. CONCLUSIONS: These studies suggest that the occurrence of human GVHD does not seem to be clearly associated with a T helper 1-type cytokine pattern.

The renal cell carcinoma lysis by a specific cytotoxic T cell clone is independent of the Fas/Fas-L cytotoxic pathway.

The expression of Fas antigen at the surface of renal cell carcinoma and the susceptibility to Fas-mediated lysis by a tumor specific CTL clone were investigated. Renal cell carcinoma cell lines expressed Fas antigen and were susceptible to apoptosis mediated by antibodies to Fas/APO1. Using RT-PCR, we further showed that these cell lines expressed mRNA for Fas deleted transmembrane region, corresponding to a soluble form of Fas/APO-1. To investigate the role of the Fas/FasL pathway in the cytotoxic response against RCC cells, we analyzed the induction of Fas-L on a tumor specific T cell clone (CTL8C2), previously generated against one RCC cell line. Fas-L expression on CTL8C2 was detected by RT-PCR after stimulation with autologous tumor cells. However, the cytotoxic activity of CTL8C2 was completely abolished when EGTA was added, suggesting that the cytolysis was mainly mediated by a Ca+2-dependent pathway, perforin/granzyme-based.

In situ demonstration of renal-cell-carcinoma-specific T-cell clones.

Using mixed lymphocyte tumor-cell culture (MLTC) in a selected renal-cell carcinoma, we derived a tumor-specific T-cell line in which Vbeta14+ and Vbeta19+ T cells represented 70% of the whole T-cell population. Selected Vbeta19+ T cells were CD8+ and exhibited a HLA-restricted specific cytotoxicity against tumor cells. Independently, 2 CTL clones were obtained by direct cloning of tumor-infiltrating lymphocytes, VIIIC2 CTL expressing a Vbeta19 and VIIB10 CTL a Vbeta13 T-cell-receptor transcript. VIIB10 lysed autologous tumor cells, normal kidney cells and EBV-transformed B cells. In contrast, VIIIC2 lysed tumor cells exclusively, demonstrating that the antigen structure recognized is tumor-specific. In addition, we used a PCR-based method to search for the presence of these CTL in situ. TCR beta chain of VIIIC2 and VIIB10 CTL were sequenced and primers complementary to their N regions were synthesized. VIIIC2 CTL constituted up to 60% of Vbeta19 transcripts in MLTC T-cell lines derived from tumor-infiltrating lymphocytes, 23% in tumor and 26% in a tumor-draining lymph node, while VIIB10 was not detected. Thus, VIIIC2 CTL was successfully derived from lymphocytes infiltrating a renal-cell carcinoma by direct cloning as well as by MLTC, probably because it was highly expanded in vivo within the tumor composing almost 2% of the TIL.

In vivo local expansion of clonal T cell subpopulations in renal cell carcinoma.

Renal cell carcinoma (RCC) is one human tumor to which the immune response may control the growth of tumor cells. These tumors are infiltrated by a large mononuclear infiltrate mainly composed of T lymphocytes. To characterize the lymphocytes infiltrating RCC, we analyzed the molecular structure of the T cell receptor (TCR) alpha and beta chains in tumor and paired peripheral blood lymphocytes from a series of 6 untreated patients. We first determined V alpha and V beta gene segment usage by PCR using a panel of V specific oligonucleotide primers (V alpha 1-w29 and V beta 1-w24). A highly diverse usage of TCR V alpha and V beta gene usage was observed in 5 of 6 tumors. In addition, the few tumor overexpressed V beta specificities detected by reverse transcription-PCR were shown to contain minor T cell expansions. Strikingly, 1 of the 6 tumor studied displayed a skewed TCR repertoire with V beta 4 transcript representing 25% of the TCR signals. Clonality of the tumor overexpressed V beta transcripts was analyzed by CDR3 size distribution analysis. In the particular tumor displaying a biased repertoire large expansions of T cell subpopulations were detected (particularly in V beta 4) specifically at the tumor site. Such T cells may be expanded locally in response to tumor antigens.

Tumor-infiltrating CD3- NK cells are more effective than CD3+ T cells in killing autologous melanoma cells.

We have studied the phenotype and functional activity of tumor-infiltrating lymphocytes (TIL) derived from eight human melanomas cultured for up to 60 d in the presence of recombinant IL-2. In the early period of the cultures, TIL were predominantly T cells of CD8+ phenotype and contained 10-30% of CD3- cells. Four of the five early TIL cultures tested in a cytotoxicity assay displayed a degree of MHC-unrestricted lysis on a series of autologous and allogenic melanoma cell lines as well as the K562 natural killer-sensitive target. With longer periods of time in culture, all TIL lines showed a decrease in lytic activity that was associated with the loss of CD3- cells. Thus, most of the killing of short-term TIL cultures appeared to be mediated by CD3- natural killer cells, whereas CD3+ T cells were found to be weak anti-tumor effectors. Even though the CD3+ T cells were not cytotoxic on K562 targets, their lytic activity (even weak) against melanoma cells appeared to be non-MHC restricted, and was blocked by anti-CD3 antibodies. In addition, cytotoxicity of the CD3+ TIL cultures was compared to that of a CD3-/NKH1+ cell line purified from peripheral blood. It was found that natural killer cells were much more potent than CD3+ TIL on the melanoma cell lines tested.

HLA-A, -B, and -DR antigens in North African patients with nasopharyngeal carcinoma.

Seventy-six North African patients (most from Algeria) affected with nasopharyngeal carcinoma (NPC) have been studied for their HLA-A, -B, and -DR phenotypes and compared with a control North African population. Antigens HLA-A3, HLA-B5 and HLA-Bw15 were found more frequently in the NPC group than in the control group (30.3% vs 17.6%, 38.2% vs 24.4% and 9.2% vs 0.8%, respectively). HLA-Aw33, HLA-B14 and HLA-DR4 were less frequent in the patients than in the controls (3.9% vs 16.8%, 1.3% vs 16% and 13.2% vs 29.1%, respectively). After correction for the number of specificities tested, these differences were not statistically significant. They were, however, more striking when compared to normal Kabyles (Algerian Berbers), a major ethnical population in Algeria, with lower incidences of the HLA-B5 antigen and of the HLA-Aw33-B14 haplotype. This could suggest, in North Africa, either the existence of MHC-linked genes of resistance or susceptibility to NPC, in Berbers especially, or a preferential occurrence of NPC in non-Berbers. Antibody titers against the Epstein-Barr virus (EBV) associated early antigen (EA) and viral capsid antigen (VCA) have been measured. No correlation was observed between HLA phenotypes and the anti-EBV serological response of the patients.