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Background and purpose: The aim was to identify the clinical and diagnostic investigations that may help to support a diagnosis of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) in patients not fulfilling the European Federation of Neurological Societies and Peripheral Nerve Society (EFNS/PNS) electrodiagnostic criteria. Methods: The data from patients with a clinical diagnosis of CIDP included in a national database were retrospectively reviewed. Results: In all, 535 patients with a diagnosis of CIDP were included. This diagnosis fulfilled the EFNS/PNS criteria in 468 patients (87.2%) (definite in 430, probable in 33, possible in three, while two had chronic immune sensory polyradiculopathy). Sixty‐seven patients had a medical history and clinical signs compatible with CIDP but electrodiagnostic studies did not fulfill the EFNS/PNS criteria for CIDP. These patients had similar clinical features and frequency of abnormal supportive criteria for the diagnosis of CIDP compared to patients fulfilling EFNS/PNS criteria. Two or more abnormal supportive criteria were present in 40 (61.2%) patients rising to 54 (80.6%) if a history of a relapsing course as a possible supportive criterion was also included. Increased cerebrospinal fluid proteins and response to immune therapy most frequently helped in supporting the diagnosis of CIDP. Response to therapy was similarly frequent in patients fulfilling or not EFNS/PNS criteria (87.3% vs. 85.9%). Conclusions: Patients with a clinical diagnosis of CIDP had similar clinical findings, frequency of abnormal supportive criteria and response to therapy compared to patients fulfilling EFNS/PNS criteria. The presence of abnormal supportive criteria may help in supporting the diagnosis of CIDP in patients with a medical history and clinical signs compatible with this diagnosis but non‐diagnostic nerve conduction studies. [ABSTRACT FROM AUTHOR]

The article focuses on a study that identify the short-term effectiveness of a short-term intensive multiple sclerosis multidisciplinary rehabilitation treatment in multiple sclerosis (MS) patients and analyzed the impact of MD rehabilitation. In the study, 212 consecutive patients were analyzed and multivariate logistic regression models have been tested. Study found that rehabilitation program is able to produce a short-term relevant improvement on clinical and functional outcome measures.

The novel human leukocyte antigen (HLA)-Cw*1609 allele was identified by sequence-based typing in a Moroccan Chaouya donor. It differs from the closest Cw*1602 by only one nucleotide (C → G) at position 244 in exon 2 (Glu to Gln at codon 58 in α1 domain). [ABSTRACT FROM AUTHOR]

After striatal injury, sprouting dopaminergic fibres grow towards and intimately surround wound macrophages which, together with microglia, express the dopaminergic neurotrophic factors glial cell line-derived neurotrophic factor (GDNF) and brain derived neurotrophic factor (BDNF). To evaluate the importance of these endogenously secreted neurotrophic factors in generating striatal peri-wound dopaminergic sprouting, the peri-wound expression of BDNF or GDNF was inhibited by intrastriatal infusion of antisense oligonucleotides for 2 weeks in mice. Knock-down of both BDNF and GDNF mRNA and protein levels in the wounded striatum were confirmed by in situ hybridization and enzyme-linked immunosorbent assay, respectively. Dopamine transporter immunohistochemistry revealed that inhibition of either BDNF or GDNF expression resulted in a marked decrease in the intensity of peri-wound sprouting. Quantification of this effect using [H³]-mazindol autoradiography confirmed that peri-wound sprouting was significantly reduced in mice receiving BDNF or GDNF antisense infusions whilst control infusions of buffered saline or sense oligonucleotides resulted in the pronounced peri-wound sprouting response normally associated with striatal injury. BDNF and GDNF thus appear to be important neurotrophic factors inducing dopaminergic sprouting after striatal injury. [ABSTRACT FROM AUTHOR]

This report describes the unknown exon 4 sequence of the rare human leukocyte antigen-Cw*0716 allele, identified in a Caucasian renal transplant recipient from Italy. This sequence is identical to the Cw*070101 allele, and this result allowed us to confirm the hypothesis of the generation of Cw*0716 allele by an interallelic recombination event between Cw*0701/0706/0718 and Cw*020202 allele. [ABSTRACT FROM AUTHOR]

A new human leukocyte antigen (HLA)-B allele, named B*3580, with an amino acid substitution at residue 156, has been identified during the sequence-based typing of a patient waiting for a hematopoietic cell transplantation. [ABSTRACT FROM AUTHOR]

This report presents a novel allele, HLA-B*4427, which was identified in a bone marrow donor of Caucasian origin, and a confirmatory sequence (B*44022). Sequence analysis revealed the new allele differs from B*44021 by a single nucleotide exchange at position 668 (C→T), which is located in exon 4. At the protein level, it is the only B*44 variant to produce an Ala in place of a Val at codon 199. Its structure suggests that it may have originated from a point mutation in B*44021 or by gene conversion with a variety of HLA-B alleles. Cloning and sequencing of the allele B*44022 revealed a sequence identical to B*44021 and B*44 exon 4, with the codon GTC (Val) in position 199. [ABSTRACT FROM AUTHOR]

HLA-A*9250 allele was identified by SBT in a Caucasian bone marrow donor. It differs from the closest A*020101 by only one nucleotide (A→G) at position 124 in exon 2 (Arg to Gly at codon 18); this is an uncommon variation at a highly conserved nucleotide position, located on the loop between S1-S2 β-sheets in α1 domain. [ABSTRACT FROM AUTHOR]

Abstract: HLA-G, a nonclassical HLA molecule with limited polymorphism has immunomodulating/tolerogenic properties. The most common polymorphism of HLA-G is a deletion/insertion of 14 bp, located at the 3′UTR region of the gene (exon 8). This polymorphism is associated with modifications of mRNA stability that can lead to variations of membrane versus solubile HLA-G expression. HLA-G may be involved in the clinical outcomes of transplantation, as evidenced by studies in hematopoietic cell transplantation. We evaluated the possible prognostic importance of 14-bp polymorphisms of HLA-G among kidney transplantation patients. Using polymerase chain reaction amplification we genotyped 124 patients (mean organ survival: 878.95 ± 595.12 days; range = 1–2565) and 98 control individuals representative of the Italian population. Products were visualized by electrophoresis on agarose gels. The results showed no differences between patients and controls. Twenty-nine patients with acute or chronic rejection or in whom clinical conditions required the use of steroid bolus treatments also showed no association with HLA-G 14-bp genotypes or alleles. The subset of patients with dyslipidemia during follow-up showed a significant decrease among the HLA-G−14/−14 genotype, compared with heterozygous (+14/−14) and nondeleted homozygous (+14/+14) genotype patients (P c = .03). These preliminary data showed that HLA-G 14-bp genotypes, although not predictive of rejection, may be useful to identify individuals at risk for the development of posttransplant complications. [Copyright &y& Elsevier]

Background: The role of genetic factors in influencing the clinical expression of multiple sclerosis (MS) is unclear. Objective: The objective of this paper is to identify genes, pathways and networks implicated in age at onset (AAO) and severity, measured using the Multiple Sclerosis Severity Score (MSSS), of primary-progressive MS (PPMS). Methods: We conducted a genome-wide association study (GWAS) of 470 PPMS patients of Italian origin:. Allelic association of 296,589 SNPs with AAO and MSSS was calculated. Pathway and network analyses were also conducted using different tools. Results: No single association signal exceeded genome-wide significance in AAO and MSSS analyses. Nominally associated genes to AAO and MSSS were enriched in both traits for 10 pathways, including: “oxidative phosphorylation” (FDRAAO=9*10−4; FDRMSSS=3.0*10−2), “citrate (TCA) cycle” (FDRAAO=1.6*10−2; FDRMSSS=3.2*10−3), and “B cell receptor signaling” (FDRAAO=3.1*10−2; FDRMSSS=2.2*10−3). In addition, an enrichment of “chemokine signaling pathway” (FDR=9*10−4) for AAO and of “leukocyte transendothelial migration” (FDR=2.4*10−3) for MSSS trait was observed, among others. Network analysis revealed that p53 and CREB1 were central hubs for AAO and MSSS traits, respectively. Conclusions: Despite the fact that no major effect signals emerged in the present GWAS, our data suggest that genetic variants acting in the context of oxidative stress and immune dysfunction could modulate the onset and severity of PPMS. [ABSTRACT FROM AUTHOR]

The aim of this study was to provide genetic and anthropological information on the Chaouya (CH), an Arabic-speaking population living in West Morocco, Atlantic coast (Settat). In 98 unrelated healthy CH volunteers, we first investigated the human leukocyte antigen (HLA) class I and II allele polymorphisms using a sequence-based typing method and examined haplotypes and relatedness of this group to other African and Mediterranean populations. The study showed the close relatedness with Tunisian population and other North Africans, together with a strong influence of various immigrations, mainly Spaniards, French, and Portuguese, as expected. Nevertheless, analysis of class II allele frequencies (afs) showed that Oromo and Amhara Ethiopian groups cluster together with the Berbers and other North Africans, confirming the relationship between these populations (Afro-Asiatic linguistic group, Hamites). South and sub-Saharan Africans cluster separately at a great distance from CH, except the sub-Saharan Bantu population from Congo Kinshasa, which shows a relatively close genetic relationship ascribable to the effect of a diversifying selection. On the other hand, considering HLA class I afs analyses, it was noteworthy that CH grouped together with sub-Saharans, showing a close genetic distance mainly with Ugandas and Kenians Luo. [ABSTRACT FROM AUTHOR]

This report describes the unknown exon 4 sequence of the rare A*7403 allele, identified in a Caucasian renal transplant cadaveric donor from Italy. This sequence is identical to that of the only known A*7401 exon 4, and this result allowed us to confirm the hypothesis of the generation of A*7403 allele from the ancestor A*7402 by point mutation in exon 2. [ABSTRACT FROM AUTHOR]

We describe an additional HLA-Cw*02 variant, HLA-Cw*0208, which has been identified in a renal transplant recipient of Caucasian origin (Italy). After performing preliminary serological typing, we analyzed exons 2 and 3 of the HLA-C locus polymorphism by cloning the amplified DNA and using a sequence-based typing method. The new allele differs from Cw*020202 by one nucleotide substitution at nucleotide 61 (G→A) of exon 2, which translates to a difference of one amino acid at residue 21 (His→Arg) of the HLA-C heavy chain. We propose that Cw*0208 was generated by a random point mutation in codon 21 from the Cw*020202 allele, or through gene conversion of Cw*020202 with another allele, probably the Cw*1205 and Cw*1602 alleles. [ABSTRACT FROM AUTHOR]

Class I human leukocyte antigen (HLA) polymorphism was examined in a Berber population from North Morocco, named Metalsa (ME). All data were obtained at high-resolution level, using sequence-based typing. The most frequent alleles were: HLA-A*0201 and A*0101; HLA-B*44 (B*4403 and B*4402); B*0801 and the B*50 allele group (B*5001 and B*5002); HLA-Cw*0602; and Cw*07 group (Cw*070101, Cw*070102, Cw*0702, Cw*0704, and Cw*0706), and Cw*040101. The novel HLA-B*570302 allele was identified. It differs at position 486 and position 855 from B*570301, resulting in synonymous Thr and Val. The analysis also evidenced some alleles common in Africans (A*3402, A*6802, A*7401, B*1503, B*4102, B*4202, B*7801, B*5802, Cw*1701, and Cw*1703) and some uncommon alleles (A*3004, B*2702, B*2703, B*5001,02, B*3503, and Cw*0706). The predominant HLA-A-Cw-B-DRB1-extended haplotypes in ME population were A*0101-Cw*0501-B*4402-DRB1*0402, A*240201-Cw*0701-B*0801-DRB1*030101, A*2301-Cw*040101-B*4403-DRB1*040501, A*0201-Cw*040101-B*4403-DRB1*1302, and A*3002-Cw*0602-B*5002-DRB1*0406. This study demonstrates a strong relatedness of ME to other Moroccan and North African populations, some characteristics of sub-Saharan Africans and evidenced the influence of various immigrations during centuries. Nevertheless, this study highlights some unique genetic traits of the ME population compared to other ethnic groups within Morocco, which could be of great interest for clinical aims, transplantation, and diseases. [ABSTRACT FROM AUTHOR]

Following injury to the mammalian CNS, axons sprout in the vicinity of the wound margin. Growth then ceases and axons fail to cross the lesion site. In this study, using dopaminergic sprouting in the injured striatum as a model system, we have examined the relationship of periwound sprouting fibers to reactive glia and macrophages. In the first week after injury we find that sprouting fibers form intimate relationships with activated microglia as they traverse toward the wound edge. Once at the wound edge, complicated plexuses of fibers form around individual macrophages. Axons, however, fail to grow further into the interior of the wound despite the presence of many macrophages in this location. We find that the expression of BDNF by activated microglia progressively increases as the wound edge is approached, while GDNF expression by macrophages is highest at the immediate wound margin. In contrast, the expression of both factors is substantially reduced within the macrophage-filled interior of the wound. Our data suggest that periwound sprouting fibers grow toward the wound margin along an increasing trophic gradient generated by progressively microglial and macrophage activation. Once at the wound edge, sprouting ceases over macrophages at the point of maximal neurotrophic factor expression and further axonal growth into the relatively poor trophic environment of the wound core fails to occur. [Copyright &y& Elsevier]

The article presents a study on the identification of the B*3812 allele. The study indicates that the sequence-based typing represents the best high resolution to observe large HLA class I and II heterogeneity. The presence of one nucleotide difference in the B*38 allele was also detected through the application of DNA sequence. It was observed that the sequence of the B*3812 allele is identical to that of B*3801.

A novel HLA-A*02 allele was detected in a Caucasian patient from central Italy, requiring a hematopoietic cell transplantation. Direct sequencing identified a variation in one nucleotide position, which was confirmed by cloning. The name A*027401 was officially assigned by the WHO Nomenclature Committee in November 2004 (AY796418, AY796419, AY796420, and HWS10002684). A*027401 differs from A*02010101 by a single G to A substitution at nucleotide position 595 in exon 3. The new variant would lead to a nonsynonymous nucleotide change (GGG to AGG) at codon 175, resulting in a basic Arg in the α-helix of the α2-domain, in place of a non-polar Gly. The presence of an uncommon variation at a highly conserved nucleotide position could have implications in unrelated hematopoietic cell transplantation. [ABSTRACT FROM AUTHOR]

This communication describes a new DRB1*11 allele identified in a familial group of Caucasian individuals from central Italy. The new sequence has been officially named DRB1*11272 by the World Health Organization (WHO) Nomenclature Committee (February 2000). It encodes an HLA antigen serologically recognized as DR11. The sequence variation of this new allele was localized to codon 77 of exon 2. It differs at position 230 from DRB1*11011 allele (A replacing C), and at position 231 from DRB1*1127 (C replacing T). At the amino acid level, the DRB1*11272 mutation is silent with respect to the DRB*1127 phenotype, coding for a synonymous asparagine. [ABSTRACT FROM AUTHOR]