糖尿病人巨细胞病毒感染的流行病学研究

为了解人类巨细胞病毒 (CMV)感染与糖尿病的关系 ,我们对 84 5例糖尿病人和 110名健康对照者CMV感染状态进行了对照研究 ,并根据糖尿病人的初发年龄和病程不同进行了分组研究。通过用ELISA对CMVIgM、IgA、IgG抗体检测发现 :糖尿病人CMVIgM、IgA、IgG抗体阳性率明显高于对照组 ;发病年龄越小或 /和病程越短的糖尿病人CMVIgM抗体阳性率明显升高 ;年龄较大或 /和病程较长的病人CMVIgG抗体检出率明显升高。该结果表明 :⑴CMV感染在糖尿病的发病机制中有一定的作用 ;⑵年龄小或 /和病程短的糖尿病人以原发性CMV感染为主。     

糖尿病人巨细胞病毒感染的流行病学研究

为了解人类巨细胞病毒(CMV)感染与糖尿病的关系,我们对845例糖尿病人和110名健康对照者CMV感染状态进行了对照研究,并根据糖尿病人的初发年龄和病程不同进行了分组研究。通过用ELISA对CMVIgM、IgA、IgG抗体检测发现:糖尿病人CMVIgM、IgA、IgG抗体阳性率明显高于对照组;发病年龄越小或 /和病程越短的糖尿病人CMVIgM抗体阳性率明显升高 ;年龄较大或 /和病程较长的病人CMVIgG抗体检出率明显升高。该结果表明:⑴CMV感染在糖尿病的发病机制中有一定的作用;⑵年龄小或 /和病程短的糖尿病人以原发性CMV感染为主。     

IgA antibody response in acute rubella determined by solid-phase radioimmunoassay.

A solid-phase radioimmunoassay (RIA) for detecting rubella virus IgA serum antibodies was developed. Purified rubella virus grown in roller cultures of Vero cells was adsorbed onto polystyrene beads. The coated beads were then incubated with dilutions of serum, and rubella IgA antibodies which attached to the virus antigen on the solid-phase were subsequently detected with 125I-labelled anti-human-alpha antibodies. The specificity of the iodinated anti-human immunoglobulins was confirmed by RIA analysis of fractions obtained by chromatography of an early convalescent serum on an agarose column. A complete separation of IgM, IgA, and IgG was observed. A total of 144 serial serum specimens from 31 adult patients with an acute rubella infection were tested for rubella IgA antibodies, and the results were compared with the RIA IgG and IgM titres reported earlier from the same specimens. The RIA IgA response was detected in each of the 31 patients and the IgA antibodies appeared almost simultaneously with the IgG and IgM antibodies. The maximum titres, which were lower than the IgG and IgM titres, were reached in about 1 week after the onset of rash. In 6 patients out of 31 the IgA antibody response was transient and persisted approximately two months, while in the remaining 25 patients the IgA antibodies persisted throughout the study period of more than 5 months. The results obtained indicate that the presence of rubella IgA antibodies in serum is not an indication for a recent rubella infection.     

Antibody-capture enzyme-linked immunosorbent assays that use enzyme-labelled antigen for detection of virus-specific immunoglobulin M, A and G in patients with varicella or herpes zoster.

Antibody-capture enzyme-linked immunosorbent assays (AC-ELISA) which use enzyme-labelled antigen were developed for detection of varicella-zoster virus-(VZV) specific IgM, IgA and IgG antibody in patients with varicella or herpes zoster and in sera from healthy individuals. All 18 patients with varicella developed a VZV-IgM and a VZV-IgG response, 17 also a VZV-IgA response. In contrast, all 19 patients with herpes zoster were shown to be positive for VZV-IgA whereas only 13 of these reacted positively for VZV-IgM. A VZV-IgM response was detected in only two sera from 100 healthy individuals and an IgA response in only one. The presence of virus-specific IgA and IgG in the cerebrospinal fluid as determined by AC-ELISA was a useful indicator of VZV infection of the central nervous system. By AC-ELISA, VZV-IgG was detected predominantly in sera from patients with acute or recent VZV infection. Only 14 sera from 100 healthy individuals were positive for VZV-IgG by AC-ELISA, whereas all were positive by an indirect ELISA. These results indicate that AC-ELISA's may be useful assays for determination for acute or recurrent VZV infection, but are not suitable for determination of past infection with this virus.     

Ingestion of Okinawa Island Vegetables Increases IgA Levels and Prevents the Spread of Influenza RNA Viruses

Background: It has been hypothesized that flavonoid ingestion stimulates immunity, promotes health, and prevents human illness. The aim of this analysis was to evaluate the association of the levels of immunoglobulin A (IgA) with the prevention of influenza infections and with the polyphenols contained in Okinawan vegetables. Methods: IgA, immunoglobulin G (IgG), immunoglobulin M (IgM), and soluble interleukin-2 receptor (sIL-2R) levels were measured in 44 outpatients who regularly ingested vegetables grown on Okinawa Island (200–300 g/day for ≥ 300 days/year) with no history of influenza infection and in 73 patients who ingested the vegetables irregularly or not at all with a history of influenza infection. Results: The patients who regularly ate Okinawan vegetables had higher IgA, IgG, and IgM levels than those who did not. On the other hand, patients who did not consume Okinawan vegetables and had influenza had lower IgA, IgG, and IgM levels. In addition, the IgA and IgG levels showed significant positive correlations with the sIL-2R levels in both groups. Conclusions: It may be beneficial to eat vegetables abundant in polyphenols every day. Secretory IgA antibodies are an important part of the immune defense against viral diseases. People who ingest Okinawan vegetables have high IgA levels and might be more likely to develop immunity against influenza RNA viruses.     

Production of IgM antibody to HHV6 in reactivation and primary infection

The cross-reaction of HHV6 antibody with that to the other herpesviruses was studied in 96 blood donors whose sera were tested for IgG antibody to human herpesvirus type 6 (HHV6), cytomegalovirus (CMV), Epstein-Barr virus (EBV), varicella zostervirus (VZV) and herpes simplex virus (HSV). No correlation was found between IgG antibody to HHV6 and that to any of the other herpesviruses in these individuals. Antibodies to HHV6 and CMV were measured in patients undergoing documented serological responses to HHV6. Eleven cases of primary HHV6 infection associated with roseola infantum in babies, 1 of whom suffered from gastroenteritis as well as pyrexia and rash, are reported. Three cases of HHV6 reactivation, 1 in a 3-year-old child and 2 in adults, 1 of whom simultaneously underwent a primary CMV infection are also reported. Our results suggest that indirect immunofluorescence is a specific way of measuring HHV6 antibody, that HHV6 IgG and IgM can be detected in the absence of antibody to CMV and that HHV6 IgM is present both in primary HHV6 infections and in reactivations.     

Serological markers of Chlamydia pneumoniae,cytomegalovirus and Helicobacter pylori infection in diabetic and non-diabetic patients with unstable angina pectoris

The possible role of inflammation in coronary artery disease (CAD) is being recognised, while markers of inflammation (e.g., CRP) and infection with Chlamydia pneumoniae (C. pneumoniae), cytomegalovirus (CMV) and Helicobacter pylori (H. pylori) have been proposed as risk factors for CAD. However, these associations require further evaluation. It is a known fact that diabetic patients suffer from impaired immune response to some pathogens and a high incidence of atherosclerosis. In this case-control study we investigated serological markers of infection with C. pneumoniae, CMV, and H. pylori in a group of 140 patients with unstable angina pectoris (UA), 52 of them having type 2 diabetes mellitus, and in a matched control group. Anamnestic (IgG) and acute infection (IgA) antibodies against the above agents were tested using ELISA or indirect immunofluorescence tests. In patients with UA we found a significantly higher seroprevalence and titres of IgG antibodies against C. pneumoniae (p = 0.04) and increased titres of IgG antibodies against CMV (p = 0.007). No differences were found in IgA antibody response to these pathogens. Antibody response to H. pylori was similar in both groups tested. In diabetic patients with UA, the frequency of group-common IgG antibodies against C. pneumoniae was higher than in the non-diabetic UA patients. The other serological markers studied were comparable in the patients with or without diabetes mellitus. Our findings confirmed association of C. pneumoniae and CMV with cardiovascular heart disease. Moreover, diabetes mellitus may predispose the patients to C. pneumoniae infection. However, serological markers observed do not indicate that destabilisation of angina pectoris is associated with acute C. pneumoniae or CMV infection. No relationship was found between UA and H. pylori infection.     

Serum immunoglobulin levels and malaria antibodies in Burkitt's lymphoma.

Data are presented to support a relationship between malaria infection and Burkitt's lymphoma in African children. IgG, IgM and IgA levels were measured in sera from Burkitt's lymphoma patients and from sex- and age-matched, nearest-neighbour controls. All three classes of immunoglobulins were present in significantly lower amounts in the sera from Burkitt's lymphoma patients than in the sera from controls. The mechanism of this apparent B-cell suppression is not yet clear. Malaria-specific IgG and IgM antibody titres were determined in the indirect immunofluorescence test. No significant difference in the IgG malaria-specific antibodies was detected between the two groups of sera. Malaria antibody levels measured using IgM specific conjugates were significantly lower in the sera from Burkitt's lymphoma patients in reactions with Plasmodium falciparum antigen. No significant difference was observed when P. malariae was used. Confirmation of this finding would serve as a positive link between Burkitt's lymphoma and P. falciparum infection.     

Specific immunoglobulin responses after varicella and herpes zoster.

The indirect immunofluorescence technique has been used to titrate the specific immunoglobulins in 200 sera from 64 patients with varicella, and 195 sera from 67 patients with herpes zoster. IgG and IgM antibodies were detected in all patients with varicella, and IgA in 59 (92%). All three classes of antibody appeared 2--5 days after the onset of the rash, increased virtually simultaneously and reached maximum titres during the second and third weeks. IgG then declined slowly, but never became undetectable and was still present in five subjects who were retested after 2--4 years; it was present in 88 out of 100 healthy young adults and probably persists indefinitely after varicella. IgA and IgM antibodies declined more rapidly and were not detected in specimens taken more than a year after the illness. IgA, however, may possibly persist in some cases since low titres were found in 8 out of 88 young adults who possessed IgG antibody and had presumably had varicella in the past. IgA responses were significantly weaker in children under the age of 6 years than in older children and adults. Six out of 67 patients with zoster were tested at various times before the onset of the rash: IgG antibody was detected in all. IgG was present in all sera taken after the onset of the rash, increased rapidly after 2--5 days, reached maximum titres during the second and third weeks and then declined slowly. IgA antibody was detected in 66 patients (99%) and IgM in 52 (78%); both types of antibody followed transient courses, as in varicella. Maximum titres of IgG and complement-fixing antibodies were greater after zoster than after varicella, but the differences were not significant. IgA and IgM titres in young adults with zoster were significantly lower than in older patients, and also lower than in young adults with varicella. Increases in varicella-zoster antibody in patients with herpes simplex virus infections consisted mainly of IgG, sometimes IgA, but never IgM.     

Induction of immune responses in pigs following oral administration of purified F4 fimbriae

An effective way of stimulating the mucosal immune system was examined in piglets, using F4 fimbriae of enterotoxigenic Escherichia coli (ETEC). It was demonstrated that purified F4 fimbriae, as opposed to ovalbumin (OVA), are powerful oral immunogens. Indeed, oral administration of purified F4 induced antigen-specific antibody-secreting cells (ASC) in the Peyer's patches, mesenteric lymph nodes (LN), blood and lamina propria 4, 7, 9 and 11 days postimmunization, respectively, indicating a stimulation of the mucosal immune system, whereas upon oral administration of OVA, no immune response was observed. Moreover, the induced F4-specific IgA and IgG antibody responses were comparable with those obtained upon oral infection with viable E. coli and intramuscular (i.m.) F4 injection, respectively. Furthermore, a priming of the mucosal immune system is better obtained by oral infection (ASC localized in mesenteric LN) than by i.m. F4 injection (ASC localized in spleen and retropharyngeal LN) since an oral boost with purified F4 induced a secondary response in the orally infected animal (mainly IgA and IgG ASC, rapid increase of IgA antibodies) while in the i.m. primed animal a secondary (more circulating antigen-specific ASC than in the unprimed animal) as well as a primary IgM and IgA response (mainly IgM ASC, slow increase of IgA antibodies), suggesting a primary mucosal response, were seen. An oral challenge of the naive control displayed a primary response (mainly IgM ASC, slow increase of IgA and IgG antibodies). The capacity of purified F4 to activate the mucosal immune system on oral administration, is of importance for the development of oral vaccines against ETEC infections.     

孕妇原发性CMV感染危险因素调查

本文分析了716例孕妇的一般资料,同时检测孕妇血中特异性CMV IgM和CMV IgG抗体。结果CMV IgM和CMV IgG抗体阳性率为6.84%和95.67%。不同孕龄、不同胎产次、有无流产史、不同职业和不同经济状况的孕妇,CMV原发感染具有显著性差异(P<0.05)。怀孕早期CMV感染率低于中、晚期,但无统计学差异(P>0.05)。并讨论了减少孕妇原发性CMV感染的措施。     

Viral etiology of obscure splenomegaly in Egyptian children

Fifty seven Egyptian children aged 1.5 to 9.5 years with mild splenomegaly (less than 3 cm below the costal margin) were screened for antibodies against the three common viruses of the Herpes group: Cytomegalovirus (CMV), Epstein-Barr (EB) and Herpes type 1 virus. A group of 57 healthy children were studied similarly. All patients were subjected to a comprehensive laboratory and clinical work up to exclude any hematological, metabolic or malignant etiology for the splenomegaly. Splenic aspirates from five cases were examined histologically and by immunohistochemistry for the antigens of CMV. Only primary or reactivation of CMV might be considered a cause of splenomegaly, as there was a statistically significant increase in the prevalence of IgM antibodies to CMV in the patients compared to normal controls (63% of patients and 19.4% of controls had IgM antibodies, P less than 0.001; 68.3% of patients and 54% of controls had IgG antibodies, P is insignificant). An almost equal proportion of children with and without splenomegaly had antibodies to EB-Viral Capsid Antigen (EBVCA) both IgG and IgM. (28% of cases and 33% of controls had IgM antibodies; 26% of patients and 21% of controls had IgG antibodies). A role of Epstein-Barr viral infection could not be ruled out in these patients. There was a higher prevalence of antibodies to Herpes type 1 virus in asymptomatic controls than in children with splenomegaly. (10% of patients and 43% of controls had IgM antibodies, 10.6% of patients and 38% of controls had IgG antibodies).     

The effect of dapsone-pyrimethamine on immunoglobulin concentrations in malaria chemoprophylaxis

Immunoglobulins IgG, IgM, IgA were estimated on 3 occasions in 59 male volunteers who were taking dapsone-pyrimethamine once weekly (dapsone: 100 mg + pyrimethamine: 12.5 mg) for malaria chemoprophylaxis. Immunoglobulins IgG and IgM measured at the 7th week of chemoprophylaxis were significantly lower than baseline values (using Students' t-test for paired data), but none of the values were below 700 mg% for IgG or 30 mg% for IgM. Immunoglobulin concentrations estimated in 45 of the 59 men 6 weeks after discontinuation of chemoprophylaxis showed a return to baseline for IgM but not IgG, which remained low. On all 3 occasions there was no significant change in the IgA concentrations. The clinical implication of these findings is not known. Further studies are required to define the effects of antimalarial drugs on the antibody response to infection and immunization.     

异基因造血干细胞移植术中施不同预处理方案后巨细胞病毒感染的临床分析

[目的]分析急性白血病异基因造血干细胞移植(Allo-HCT)中接受两种不同预处理方案的患者巨细胞病毒(CMV)感染和发病情况,评价预处理方案。[方法]对2004年3月～2011年3月在四川大学华西医院接受Allo-HCT的57例急性白血病患者进行回顾性分析,据预处理方案不同分为A组和B组,A组为白消安、环磷酰胺、阿糖胞苷方案(BuACy方案),有22例;B组为白消安、氟达拉滨、阿糖胞苷方案(BFA方案),有35例。根据临床表现将CMV病毒感染分为CMV血症和CMV病。CMV血症定义为有CMV病原学证据(CMV-DNA检测阳性和/或CMV-IgG,IgM均阳性)但无CMV感染症状;CMV病定义为有CMV病原学证据及病毒临床损害表现。[结果]移植后共发生22例CMV感染(14例CMV血症,8例CMV病),其中A组感染10例(45.5%),包括CMV病7例(31.8%);B组感染12例(34.3%),包括CMV病1例(2.86%)。通过卡方检验,两组患者CMV感染率差异无统计学意义(χ2=0.318,P﹥0.05);但CMV病发生率差异有统计学意义(χ2=7.14,P﹤0.05)。[结论]在异基因外周血造血干细胞移植术中通过采用BFA方案预处理能减少CMV病发生率,改善患者预后。     

Secretor status and humoral immune responses to Neisseria lactamica and Neisseria meningitidis.

Non-secretors of ABO blood group antigens are over-represented among patients with meningococcal diseases. Lower levels of secretory IgA reported for non-secretors have been suggested to compromise mucosal defences. Total serum and salivary IgG, IgA and IgM and levels of these isotypes specific for Neisseria lactamica and five isolates of meningococci were determined by ELISA for 357 pupils and staff of a secondary school in which an outbreak of meningitis occurred. There were no differences in total or specific levels of serum IgG, IgA or IgM or salivary IgG or IgA of secretors compared with non-secretors. Non-secretors had significantly lower levels of salivary IgM (P = 0.022). A similar pattern was observed for levels of IgM specific for N. lactamica and five meningococcal isolates. The significance of these results is discussed with reference to the role of secretory IgM in protection of mucosal surfaces in infants.     

Immunologic markers of the risk of cytomegalovirus infection among immunosuppressed patients

ELISA and complement fixation test (CF) were compared for the determination of the Cytomegalovirus (CMV) humoral immune status of donors and recipients before and after graft. ELISA-IgG was more sensitive than the CF test and permitted a better identification of the high risk donors and recipients. The presence of IgM antibodies in the recipient at the day of transplantation is an index of greater susceptibility to chronic or recurrent infection at a later date. In primary renal allograft recipient the detection of specific IgM antibodies by ELISA provides more rapid diagnosis than that by CF. In bone marrow transplants, ELISA-IgM showed a better correlation with the virus isolation than the CF test. In the reinfected renal allograft patients the presence of IgM was related to clinical manifestations. Using ELISA, specific decreases of CMV antibody titers were detected before virus isolation.     

南京地区育龄女性TORCH感染状况调查

目的调查在南京大学医学院附属鼓楼医院进行孕前筛查和产前普查的育龄女性的TORCH感染情况,分析不同季节、不同年龄段人群TORCH感染的特征,为该地区育龄女性的预防保健提供参考依据。方法采用酶联免疫吸附试验对3 340例孕前及孕期妇女进行血清中TORCH特异性抗体IgM、IgG检测,根据季节、年龄分组比较TORCH不同病原体感染率的差异。结果 3 340例受检者中总IgM阳性率为2.6%,巨细胞病毒（CMV）的IgM阳性（近期感染）率和IgG阳性（既往感染）率分别为1.05%和65.14%;弓形虫（TOX）、风疹病毒（RV）和CMV IgM的检出率均在夏季最高,夏季TOX和RV IgM阳性率分别为1.38%和1.30%,显著高于其他3个季节（P〈0.01）;20-25岁年龄组TOX IgM检出率（1.08%）显著高于26-30岁组（0.36%）（P〈0.05）;CMV IgM的阳性率在20-25岁组最高,为1.49%,与31-45岁组（0.47%）差异有统计学意义（P〈0.05）。结论育龄女性TORCH感染以CMV最多见,相关病原体感染具有季节性和年龄差异,有必要有针对性地加强预防保健,并积极做好TORCH特异性抗体的检测和监测。     

Serological differentiation between past and present infection in hepatic amoebiasis

The indirect fluorescent antibody (IFA) test and the amoebic gel diffusion (AGD) test were assessed as tools for differentiating between past and present infection in invasive amoebiasis; in the case of the IFA test the Entamoeba histolytica-specific IgG and IgM were monitored. In a pilot study in which sera from 56 patients with suspected invasive amoebiasis were tested the IgM was positive in 40% of confirmed intestinal and 83% of confirmed hepatic cases, the IgG and AGD were positive in all confirmed cases. A subsequent study was then carried out, in which the tests were used to monitor longitudinally antibody levels of patients with confirmed amoebic liver abscess, from the time of admission to hospital, to one year after successful treatment. The specific IgM levels became negative sooner than the IgG or AGD, with more than half the subjects giving negative results at six months and all cases becoming negative 46 weeks after treatment. The results of this study suggest that the presence of specific IgM, together with specific IgG and a strongly positive AGD test, is indicative of an active infection; conversely, when the IgM is negative, while the other tests are positive, active disease was usually absent.     

Specific IgE response in patients with brucellosis

In the search to find discriminative serological markers to differentiate between patients with acute brucellosis and those with chronic brucellosis, an enzyme-linked immunosorbent assay (ELISA) was used to determine and compare the brucella-specific IgE response in 80 sera from patients with acute brucellosis, 37 sera from patients with chronic brucellosis, 26 sera from patients with positive blood cultures for bacteria other than brucella and 51 sera from healthy controls. The IgE findings were compared to brucella-specific IgG, IgM, IgA and IgG1-4 demonstrated by ELISA, and to microagglutination test (MAT) results. Elevated (positive) antibrucella IgE titres were detected in 89 and 81% of sera from patients with acute and chronic brucellosis respectively. The predominant antibodies found in patients with acute brucellosis were of the IgG, IgM, IgA, IgE, IgG1 and IgG3 types while in chronic brucellosis IgG, IgA, IgE and IgG4 were found. Although IgE can be detected in patients with brucellosis, it does not discriminate between the acute and chronic stages of the disease.     

Antibody to the nonstructural protein NS1 of Japanese encephalitis virus: potential application of mAb-based indirect ELISA to differentiate infection from vaccination

An indirect enzyme-linked immunosorbent assay (ELISA) was developed to detect and differentiate the antibody responses to Japanese encephalitis (JE) virus nonstructural protein NS1 between infected and vaccinated individuals. The results showed that all convalescent sera from JE patients contained NS1-specific IgG antibodies, while 65 and 40% of these sera showed detectable NS1-specific IgM and IgA antibodies, respectively. Specificity analysis showed that NS1-specific IgM and IgA antibodies from JE patients do not cross-react to dengue virus NS1 glycoprotein, while IgG antibodies from 10% of JE patients showed significant cross-reaction to dengue virus NS1 glycoprotein. To differentiate infection from vaccination, the immune sera from 24 children vaccinated with inactivated JE vaccine were analyzed. The data showed that none of these immune sera had detectable NS1-specific IgG antibodies. The results demonstrated the potential application of JE NS1-specific indirect ELISA to differentiate infection from vaccination.