Bibliometric analysis of subject trends and knowledge structures of gut microbiota.

BACKGROUND: Gut microbiota is an emerging field of research, with related research having breakthrough development in the past 15 years. Bibliometric analysis can be applied to analyze the evolutionary trends and emerging hotspots in this field. AIM: To study the subject trends and knowledge structures of gut microbiota related research fields from 2004 to 2018. METHODS: The literature data on gut microbiota were identified and downloaded from the PubMed database. Through biclustering analysis, strategic diagrams, and social network analysis diagrams, the main trend and knowledge structure of research fields concerning gut microbiota were analyzed to obtain and compare the research hotspots in each period. RESULTS: According to the strategic coordinates and social relationship network map, Clostridium Infections/microbiology, Clostridium Infections/therapy, RNA, Ribosomal, 16S/genetics, Microbiota/genetics, Microbiota/immunology, Dysbiosis/immunology, Infla-mmation/immunology, Fecal Microbiota Transplantation/methods, Fecal Microbiota Transplantation can be used as an emerging research hotspot in the past 5 years (2014-2018). CONCLUSION: Some subjects were not yet fully studied according to the strategic coordinates; and the emerging hotspots in the social network map can be considered as directions of future research.

Human cytomegalovirus UL141 protein interacts with CELF5 and affects viral DNA replication.

Human cytomegalovirus (HCMV) infection is the primary viral cause of congenital abnormalities and mental retardation in newborns. The HCMV UL141­encoded glycoprotein has been previously revealed to inhibit the cell­surface expression of cluster of differentiation (CD)155, CD122, tumor necrosis factor­related apoptosis­inducing ligand death (TRAIL)­receptor 1 (R1) and TRAIL­receptor 2 (R2), thus protecting virally­infected cells by allowing them to escape natural killer cell­mediated cytotoxicity. The present study investigated the interaction between HCMV UL141 and human fetal brain cDNA to elucidate the possible effects of UL141 on the nervous system. The findings of the current study demonstrate that the HCMV UL141 protein directly interacts with the human protein CUGBP Elav­like family member 5 (CELF5) via yeast two­hybrid screening, this interaction was confirmed by glutathione S­transferase pull­down and co­immunoprecipitation assays. Additionally, the present study demonstrated that the UL141 protein co­localizes with CELF5 in the cytoplasm of 293 cells using fluorescence confocal microscopy. CELF5 overexpression in a stably­expressing cell line significantly increased viral DNA copy number and titer in HCMV­infected U373MG cells. However, reducing CELF5 expression via specific small interfering RNAs did not affect viral DNA copy number or titer in HCMV­infected cells. The current findings suggest that the interaction between UL141 and CELF5 may be involved in modulating viral DNA synthesis and progeny production. Therefore, CELF5 may represent a possible mechanism for regulation of HCMV genomic DNA synthesis, which is a key step during HCMV infection leading to neurological disease.

Identification of immediate early gene X-1 as a cellular target gene of hcmv-mir-UL148D.

Human cytomegalovirus (HCMV) is a herpesvirus that causes congenital diseases and opportunistic infections in immunocompromised individuals. Its functional proteins and microRNAs (miRNAs) facilitate efficient viral propagation by altering host cell behavior. The identification of functional target genes of miRNAs is an important step in the study of HCMV pathogenesis. HCMV encodes at least 14 miRNAs, including hcmv-mir-UL148D, which resides in the HCMV UL/b' region. hcmv-mir-UL148D is the only miRNA encoded by the HCMV UL/b' region; however, its targets and functional effects have not yet been eludidated. In this study, hybrid-PCR screening was used to identify target genes and dual luciferase reporter assay was used to evaluate the binding effect of hcmv-miR-UL148D to the 3' untranslated region (3'UTR) of IEX-1. In addition, western blot analysis was used to detect the expression kinetics of IEX-1 protein and apoptosis assay was used to identify the effects of hcmv-miR-UL148D on cell apoptosis. The hybrid-PCR results showed that only one binding site in the 3'UTR of the cellular gene, human immediate early gene X-1 (IEX-1), was completely complementary to an 11 nucleotide (nt) sequence in the 5' terminus of hcmv-mir-UL148D, including the entire seed region. The binding site was demonstrated to be functional by dual luciferase reporter assay with a 47% repression of the relative luciferase activity. In an in vitro system of human embryonic kidney 293 (HEK293) cells, the ectopically expressed hcmv-mir-UL148D exhibited a downregulatory effect on IEX-1 expression, and decreased the cell apoptosis induced by transfected IEX-1. Our data demonstrate that hcmv-mir-UL148D targets the cellular gene, IEX-1, downregulating its expression and thus results in anti-apoptotic effects.

Variations of human papillomavirus type 58 E6, E7, L1 genes and long control region in strains from women with cervical lesions in Liaoning province, China.

Infection with certain types of human papillomaviruses (HPVs) is a risk factor for the development of cervical cancer. HPV type 58 (HPV 58) is prevalent among Chinese women. The intratype sequence variants differ in oncogenic potential and their prevalences vary across geographic regions. The objective of this study was to analyze the variations of HPV 58 E6, E7, L1 genes and long control region (LCR) in a large samples collected from northeastern Chinese women with cervical lesions. A total of 2938 cervical samples were collected and tested for HPV type using a chip hybridization assay. The E6, E7, L1 genes and LCR of HPV 58 strains were amplified and the amplicons were subjected to direct nucleotide sequencing for variation identification. A total of 235 specimens were HPV 58 positive. High proportions of HPV 58 E6 (83.8%), E7 (76.7%), L1 (90.8%) genes and LCR (91.4%) variants were identified in strains from Chinese women. The most frequently observed variations were C307T (52.4%) in E6, T744G (74.9%) in E7, A6014C (56.9%) in L1 genes and C7266T, A7714G (55.2%) in LCR. For the E6 gene, nine nucleotide variations were identified. Among them, the A140G (T11A), A184C (E25D), G266C (V53L) and A313G were novel variations. Sequencing of the E7 gene revealed four typical nucleotide changes: G761A (G63D), G694A (G41R), T803C (V77A) and T744G. In the L1 gene, 39 nucleotide variations and 13 amino acid substitutions were identified. Among these mutations, 21 variations are reported here for the first time. Lineage A of HPV 58 was found in 142 of 174 strains (81.6%). The most prevalent HPV 58 variants in Chinese northeastern women belongs to lineage A. Novel variations in E6 and L1 genes were also reported. These findings provide new data regarding E6 and L1 gene variations of HPV 58 from women in northeast China.

Interaction between human cytomegalovirus UL136 protein and ATP1B1 protein

Interplay between the host and human cytomegalovirus (HCMV) has a pivotal role in the outcome of infection. A region (referred to as UL/b’) present in the Toledo strain of HCMV and low passage clinical isolates contains 19 additional genes, which are absent in the highly passaged laboratory strain AD169. Products of the UL/b’ genes may determine the manifestations of HCMV infection in vivo. However, little is known about the host factors, which interact with UL/b’ proteins. This study was conducted to investigate the function of the HCMV UL136 protein. By yeast two-hybrid screening, the β1 subunit of the host Na+/K+-ATPase (ATP1B1) was identified to be a candidate protein, which interacts with the HCMV UL136 protein. The interaction was further evaluated both in vitro by pull-down assay and in vivo by immunofluorescent co-localization. The results showed that the UL136 protein can interact with ATP1B1 in vitro. Co-localization of UL136-EGFP and ATP1B1-DsRed in cell membranes suggests that ATP1B1 was a partner of the UL136 protein. It can be proposed that the HCMV UL136 protein may have important roles in processes such as cell-to-cell spread, and in maintaining cell osmotic pressure and intracellular ion homeostasis during HCMV infection.

Interaction between human cytomegalovirus UL136 protein and ATP1B1 protein.

Interplay between the host and human cytomegalovirus (HCMV) has a pivotal role in the outcome of infection. A region (referred to as UL/b') present in the Toledo strain of HCMV and low passage clinical isolates contains 19 additional genes, which are absent in the highly passaged laboratory strain AD169. Products of the UL/b' genes may determine the manifestations of HCMV infection in vivo. However, little is known about the host factors, which interact with UL/b' proteins. This study was conducted to investigate the function of the HCMV UL136 protein. By yeast two-hybrid screening, the ß1 subunit of the host Na+/K+-ATPase (ATP1B1) was identified to be a candidate protein, which interacts with the HCMV UL136 protein. The interaction was further evaluated both in vitro by pull-down assay and in vivo by immunofluorescent co-localization. The results showed that the UL136 protein can interact with ATP1B1 in vitro. Co-localization of UL136-EGFP and ATP1B1-DsRed in cell membranes suggests that ATP1B1 was a partner of the UL136 protein. It can be proposed that the HCMV UL136 protein may have important roles in processes such as cell-to-cell spread, and in maintaining cell osmotic pressure and intracellular ion homeostasis during HCMV infection.

[Transcription pattern of UL131A-128 mRNA in HCMV clinical strains].

OBJECTIVE: To study and research the transcription pattern of UL131A-128 mRNA in human cytomegalovirus (HCMV) clinical low passage strains. METHODS: The UL131A-128 mRNAs of from different clinical strains and kinetic periods were amplified using 3' RACE and analyzed by sequencing. Meanwhile, clones containing UL131A-128 transcripts in a HCMV cDNA library of clinical strain were selected and sequenced. RESULTS: It is successful to obtain the transcription pattern of UL131A, UL130 and UL128 gene in HCMV clinical low passage strains, the UL131A gene consisted of two exons and the coding region of UL130 gene was not interrupted by any intron in the region as reported before. However, the transcript of UL128 gene showed two patterns, one pattern consisted of the three exons, the length is 519bp, and the other one contained the three exons and the sequence of the first intron further, the length is 642bp. The quantities of UL128 transcript containing the sequence of the first intron were higher than that of transcript only containing the three exons in the studied clinical strains at all kinetic classes. It was demonstrated that the UL131A-128 mRNA were expressed with immediately early, early and late kinetics. The result of 3'RACE and HCMV cDNA library of clinical strain is conformity. CONCLUSIONS: Our results demonstrated that the UL131A, UL130 and UL128 genes were transcribed with 3'-coterminal, although the initiation points of their mRNA may be different. The variation of the transcripts found in our study indicated complex nature of transcription of UL131A-128 genes in HCMV clinical strains.

Characteristics of HPV prevalence among women in Liaoning province, China.

OBJECTIVES: To investigate the prevalence rates of specific human papillomavirus (HPV) types infecting women in Liaoning Province, China. METHODS: Specimens from 4780 patients with cervical disease and 165 age-matched controls were tested for HPV genotypes using a chip hybridization assay. RESULTS: The infection rates were 35.66% for patients with cervicitis, 54.61% for those with ASCUS, 64.14% for those with CIN, 83.76% for those with cervical cancer in situ, and 83.12% for those with invasive cervical cancer. The most common HPV genotype was HPV-16, followed by HPV-58, HPV-52, HPV-33, HPV-53, and HPV-31. There were 1529 single and 731 multiple infections among the 4780 patients. Single infections with high-risk genotypes were associated with various cervical diseases. HPV-16 was present in 399 of the patients with multiple infections. CONCLUSION: Compared with prevalence rates for other populations, the rates of specific HPV types infecting women are different in Liaoning Province of China.

Human cytomegalovirus UL138 open reading frame is highly conserved in clinical strains.

OBJECTIVE: To investigate the variability of human cytomegalovirus (HCMV) UL138 open reading frame (ORF) in clinical strains. METHODS: HCMV UL138 ORF was amplified by polymerase chain reaction (PCR) and PCR amplification products were sequenced directly, and the data were analyzed in 19 clinical strains. RESULTS: UL138 ORF in all 30 clinical strains was amplified successfully. Compared with that of Toledo strain, the nucleotide and amino acid sequence identities of UL138 ORF in all strains were 97.41% to 99.41% and 98.24% to 99.42%, respectively. All of the nucleotide mutations were substitutions. The spatial structure and post-translational modification sites of UL138 encoded proteins were conserved. The result of phylogenetic tree showed that HCMV UL138 sequence variations were not definitely related with different clinical symptoms. CONCLUSION: HCMV UL138 ORF in clinical strains is high conservation, which might be helpful for UL138 encoded protein to play a role in latent infection of HCMV.

[Polymorphism analysis of human cytomegalovirus UL150 gene in low passage clinical isolates].

OBJECTIVE: To investigate the polymorphism of human cytomegalovirus UL150 gene in low passage clinical isolates and try to study the relationship between the polymorphism and different pathogenesis of congenital HCMV infection. METHODS: PCR was performed to amplify the entire HCMV UL150 gene region of 29 clinical isolates, which had been proven containing detectable HCMV-DNA by using FQ-PCR. PCR amplification products were sequenced directly and the data were analysed. RESULTS: 25 among 29 isolates were amplified and 18 isolates were sequenced successfully. By comparison with the sequence of Toledo and Merlin, the length of UL150 ORFs in all 18 clinical isolates was similar to that of Merlin than Toledo. CONCLUSION: HCMV UL150 DNA and deduced amino acid sequences is hypervariability.

Sequence conservation of human cytomegalovirus UL140 open reading frame in clinical strains.

OBJECTIVE: To investigate the variability of human cytomegalovirus (HCMV) UL140 open reading frame (ORF) in clinical strains, and to explore the relationship between the variability of UL140 ORF and different symptoms of HC-MV infection. METHODS: HCMV UL140 ORF was amplified by polymerase chain reaction and sequenced selectedly in 30 clinical strains. RESULTS: UL140 ORF of all clinical strains was amplified successfully. Compared with that of Toledo strain, the nucleotide and amino acid sequence identities among all strains were 96.5%-100.0% and 95.2%-100.0%, respectively. All of the nucleotide changes were substitutions. The post-translational modification sites were conserved. The result of phylogenetic tree showed that the strains did not cluster according to different clinical symptoms. CONCLUSION: HCMV UL140 ORF in clinical strains is highly conserved, which may play an important role in HC-MV infection.

[Polymorphism of human cytomegalovirus UL134 gene in low-passage clinical isolates].

OBJECTIVE: Human cytomegalovirus (HCMV) displays genetic polymorphisms. Nineteen open reading frames (ORFs, UL133-UL151) found in the Toledo strain of HCMV and other low-passage clinical isolates may be essential for viral infection. This study aimed to analyze the polymorphism of HCMV UL134 gene in clinical isolates and explore the relationship between the polymorphism and HCMV infection. METHODS: PCR was performed to amplify entire UL134 region in 32 clinical isolates, which had been proven as HCMV-DNA positive by FQ-PCR. PCR products were sequenced. RESULTS: All of the 32 isolates were amplified and sequenced successfully. HCMV UL134 gene was highly conserved in the clinical isolates. UL134 ORF and its predicted protein in the clinical strains displayed 96.4%-98.3% nucleotide identity and 92.7%-94.9% amino acid identity respectively compared to those in the Toledo strain. A new posttranslational modification site, sulfationcamp (SUL) site, was found in UL134 protein of all of the clinical isolates except 35j. CONCLUSIONS: HCMV UL134 gene in clinical isolates was highly conserved. No substantial relation was found between UL134 gene and HCMV infectious diseases.

Genetic polymorphism of UL144 open reading frame of human cytomegalovirus DNA detected in colon samples from infants with Hirschsprung's disease.

AIM: To explore the genetic diversities of UL144 open reading frame (ORF) of cytomegalovirus DNA detected in colon tissue from infants with Hirschsprung's disease (HD) by sequencing UL144 DNA in 23 aganglionic colon tissue and 4 urine samples from 25 HD infants. METHODS: Nest PCR was performed for amplification of the UL144 gene. The UL144 gene was analyzed with softwares, such as DNAclub, BioEdit, PROSITE database, and DNAstar. RESULTS: The strains from HD patients were distributed among three genotypes of UL144: group 1A (64%), group 2 (24%), and group 3 (12%). The UL144 genotypes between strains from HD and control group were compared by chi square test (c2 = 1.870, P = 0.393). Strains from the colon were sporadically distributed in UL144 genotypes. CONCLUSION: There are genetic diversities of UL144 ORF in colon tissue of infants with HD. However, cytomegalovirus UL144 genotypes are not associated with clinical manifestations of HD.

Genetic variability of human cytomegalovirus UL132 gene in strains from infected infants.

Human cytomegalovirus (HCMV) displays genetic polymorphisms. HCMV infects a number of organs and cell types, leading to the hypothesis that HCMV disease and tissue tropism may be related to specific sequence variability. A gene in UL/b' of HCMV, UL132 open reading frame (ORF), encodes glycoprotein (gpUL132) which is identified as a low-abundance structural component of HCMV. In this study, the sequence variability of the UL132 gene was studied in 30 clinical strains. The results showed that a large number of nucleotide non-synonymous substitutions occurred in the UL132 ORF, particularly in the 5' half, in comparison to the UL132 of reference strain, Toledo. The UL132 variants of the clinical strains were clustered clearly into three major groups in the phylogenetic tree: G1(10/30), G2(9/30), and G3(11/30). The precise definition of UL132 genotypes and their putative functions would be helpful in a better understanding of the HCMV.

High variability of human cytomegalovirus UL150 open reading frame in low-passaged clinical isolates.

OBJECTIVE: To investigate the polymorphism of human cytomegalovirus (HCMV) UL150 open reading frame (ORF) in low-passaged clinical isolates, and to study the relationship between the polymorphism and different pathogenesis of congenital HCMV infection. METHODS: PCR was performed to amplify the entire HCMV UL150 ORF region of 29 clinical isolates, which had been proven containing detectable HCMV-DNA using fluorescence quantitative PCR. PCR amplification products were sequenced directly, and the data were analyzed. RESULTS: Totally 25 among 29 isolates were amplified, and 18 isolates were sequenced successfully. HCMV UL150 ORF sequences derived from congenitally infected infants were high variability. The UL150 ORF in all 18 clinical isolates shifted backward by 8 nucleotides leading to frame-shift, and contained a single nucleotide deletion at nucleotide position 226 compared with that of Toledo strain. The nucleotide diversity was 0.1% to 6.8% and the amino acid diversity was 0.2% to 19.2% related to Toledo strain. However, the nucleotide diversity was 0.1% to 6.4% and amino acid diversity was 0.2% to 8.3% by compared with Merlin strain. Compared with Toledo, 4 new cysteine residues and 13 additional posttranslational modification sites were observed in UL150 putative proteins of clinical isolates. Moreover, the UL150 putative protein contained an additional transmembrane helix at position of 4-17 amino acid related to Toledo. CONCLUSION: HCMV UL150 ORF and deduced amino acid sequences of clinical strains are hypervariability. No obvious linkage between the polymorphism and different pathogenesis of congenital HCMV infection is found.

Sequence variability of human cytomegalovirus UL143 in low-passage clinical isolates.

BACKGROUND: Human cytomegalovirus (HCMV) infects a number of organs and tissues in vivo. The different symptoms and tissue tropisms of HCMV infection perhaps result from genetic polymorphism. A new region of DNA containing at least 19 open reading frames (ORFs) (denoted UL133 to 151) was found in the low-passage HCMV clinical strain, Toledo, and several other low-passage clinical isolates, but not present in the HCMV laboratory strain, AD169. One of these genes, UL143, was studied to explore the sequence variability of UL143 ORF in HCMV clinical isolates and examine the possible association between gene variability and the outcome of HCMV infection. METHODS: The UL143 gene of the strains obtained from suspected congenitally HCMV-infected infants was amplified by polymerase chain reaction (PCR) and sequenced. RESULTS: Nineteen sequences of the strains were divided into 2 major groups, G(1) (n = 16) and G(2) (n = 3). All of the sequences had frame-shift mutation compared to Toledo. Nucleotide polymorphisms conferred substantial amino acid substitutions when compared with Toledo. All 16 UL143 putative proteins of the strains in G(1) had a new myristylation site and loss of two PKC sites owing to missense mutations. No convincing relationships were observed between the presence of HCMV disease and the UL143 sequence group. CONCLUSIONS: HCMV-UL143 existed in low passage isolates. Sequence variability caused by frame-shift mutation was found in all HCMV clinical strains. No obvious linkage was observed between UL143 polymorphisms and the outcome of suspected congenital HCMV infection.

Sequence variability of human cytomegalovirus UL146 and UL147 genes in low-passage clinical isolates.

OBJECTIVES: Human cytomegalovirus (HCMV) infects a number of organs and cell types in vivo. The different symptoms and tissue tropisms of HCMV infection perhaps result from the genetic polymorphism. A new region of DNA containing at least 19 open reading frames (ORFs - denoted UL133-151) was found in the low-passage HCMV clinical strain Toledo and several other low-passage clinical isolates, but not present in the HCMV laboratory strain AD169. Two of these genes, UL146 and UL147, encode proteins with sequence characteristics of CXC (alpha) chemokines, suggesting that they might influence the behavior of neutrophils during infection. This research was to study the sequence variability of UL146 and UL147 ORFs in HCMV clinical isolates and examine the possible associations between gene variability and the outcome of HCMV infection. METHODS: UL146 and UL147 genes from strains obtained from suspected congenitally HCMV-infected infants were PCR amplified and sequenced. RESULTS: High variability was found in UL146 and UL147 gene among HCMV clinical strains. However, the alpha chemokine motif in UL146 and UL147 genes was conserved in almost all sequences. According to the phylogenetic analysis, all sequences of UL146 in clinical isolates could be divided into three groups. All strains from congenital megacolon infants existed in G2A only, and all from asymptomatic infants existed in G2B peculiarly. CONCLUSIONS: Sequence variability among HCMV clinical strains may affect the ability of UL146 and UL147 to attract human neutrophils and influence viral dissemination. No obvious linkage was observed between UL146 polymorphisms and outcome of suspected congenital HCMV infection.

Human cytomegalovirus (HCMV) UL139 open reading frame: Sequence variants are clustered into three major genotypes.

Human cytomegalovirus (HCMV) infects a number of organs and cell types, leading to the hypothesis that HCMV disease and tissue tropism may be related to specific sequence variability. This study examined the genomic variability of a new polymorphic locus in HCMV, UL139 open reading frame (ORF). Detailed analysis showed that a large number of nucleotide insertions and non-synonymous substitutions occurred in the UL139 ORF, particularly in the 5' half, using the Toledo strain as the reference sequence. The UL139 variants were not distributed randomly, but were clustered clearly into three major groups: G1 (G1a, G1b, and G1c), G2 (G2a, G2b), and G3. In this study, it was found that the predicted UL139 product shared sequence homology with human CD24, a signal transducer modulating B-cell activation responses, and the sequences in G1c contained a specific attachment site of prokaryotic membrane lipoprotein lipid. The precise definition of UL139 genotypes and its putative function would be helpful in understanding better HCMV.

Structure and variability of the UL149 open reading frame from low-passage clinical isolates of human cytomegalovirus.

Human cytomegalovirus (HCMV), a ubiquitous herpesvirus, causes a lifelong subclinical infection in healthy adults but leads to significant morbidity and mortality in neonates and immunocompromised individuals. A region (referred to as UL/b') present in the Toledo strain of HCMV and low passage clinical isolates contains 19 additional genes, which are absent in the highly passage laboratory strain AD169. One of these genes, UL149 open reading frame, was amplified by PCR and sequenced from isolates obtained from infants with congenital HCMV infection, to determine whether genetic variation of this gene could influence the signs of the virus infection. The major finding is that the UL149 is a variable gene in all 26 clinical isolates, and the sequences from clinical isolates were classified into three major groups. It is concluded that the HCMV UL149 sequence is variable at the nucleotide level and it might play an important role in HCMV infection.

Polymorphism of the mouse gene for the interleukin 10 receptor alpha chain (Il10ra) and its association with the autoimmune phenotype.

Several studies suggest that interleukin (IL)-10 pathway is involved in murine lupus, while no linkage of IL-10 gene polymorphism to disease susceptibility has been reported in studies with lupus-prone mice. Since IL-10 functions through the specific IL-10 receptor alpha (IL-10RA) chain and the IL-10RA gene (Il10ra) is linked to the susceptibility loci of atopic dermatitis and Crohn's disease identified using mouse models, we supposed that IL-10RA might be involved in murine lupus. By flow cytometry analysis, we found that NZW mice, one of the parental strains of lupus-prone (NZBxNZW) F1 mice, express extremely low levels of IL-10RA compared with NZB mice, the other parental strain, and the healthy BALB/c and C57BL/6 mice. Sequence analyses of Il10ra cDNA of NZW mice showed multiple nucleotide mutations compared with that of NZB and C57BL/6 strains, some of which would result in amino acid substitutions in the IL-10RA protein. Lupus-prone MRL mice shared the same polymorphism with NZW. Analyses using (NZBxNZW) F1xNZB backcross mice showed that high serum levels of IgG antichromatin antibodies were regulated by a combinatorial effect of the NZW Il10ra allele and a heterozygous genotype for Tnfa microsatellite locus. Our data suggest that the polymorphic NZW-type Il10ra may be involved in the pathologic production of antichromatin antibodies and, if so, may contribute in part to the development of systemic lupus erythematosus as one susceptibility allele.