Rise Of IgM Research Articles

2186. Differentiation of Severe Fever with Thrombocytopenia Syndrome from Scrub Typhus

BackgroundSFTS and scrub typhus have similar clinical features and difficult to differentiate. Thus, a study to develop a scoring system to differentiate between two diseases in a clinical setting before the confirmation of laboratory results was reported by Kim et al. However, the statistical power could be low because of low numbers of cases (21 SFTS, 91 scrub typhus), our study analyzed by increasing the number of cases to overcome these limitations.MethodsWe retrospectively collected data from 183 SFTS and 178 scrub typhus patients who visited the 21 hospitals in South Korea between October, 2013 and November, 2017. The study protocol was approved by the IRB of each institution. SFTS was diagnosed through detection of SFTS viral RNA using RT–PCR. Scrub typhus was diagnosed either detection of 56-kDa antigen of O. tsutsugamushi using nested PCR or ≥ 4 fold rise in IgM or IgG titer using indirect IFA. Statistical analyses were performed by using SPSS and Medcalc.ResultsTo differentiate SFTS from scrub typhus, we applied the scoring system proposed by Kim et al. After multivariable logistic regression, altered mental status, leukopenia, prolonged aPTT, and normal CRP(≤ 1.0 mg/dL) were significantly associated with SFTS compared with scrub typhus. Each variable was scored by 1 point, with a total score of 0–4 points, the optimal cutoff value was > 1 for the ROC curve. A score > 1 had 92% sensitivity, 96% specificity for diagnosis of SFTS, with a ROC AUC of 0.974. Because the sensitivity was less than 95%, we changed the normal CRP criteria to ≤ 3.0 mg/dL. The modified scoring system had 97% sensitivity, 96% specificity for diagnosis of SFTS, with an AUC of 0.983, and it showed a statistically higher accuracy than original scoring system (P = 0.0487). In this study, four factors for predicting SFTS were newly developed: leukopenia, prolonged aPTT, normal CRP (≤3.0 mg/dL), and elevated CK (>1,000 IU/L). Our study scoring system had 97% sensitivity, 98% specificity for diagnosis of SFTS, with an AUC of 0.992, and it showed a statistically higher accuracy than original scoring system (P = 0.0308).ConclusionIn conclusion, we can easily differentiate SFTS from scrub typhus by using our scoring system of leukopenia, prolonged aPTT, normal CRP, and elevated CK in the endemic area. Disclosures All authors: No reported disclosures.

Rickettsia felisInfections and Comorbid Conditions, Laos, 2003–2011

<i>Rickettsia felis</i>Infections and Comorbid Conditions, Laos, 2003–2011

A Phase II Trial of Ofatumumab in Subjects with Waldenstrom's Macroglobulinemia,

A Phase II Trial of Ofatumumab in Subjects with Waldenstrom's Macroglobulinemia,

A Phase II Trial of Ofatumumab In Subjects with Waldenstrom's Macroglobulinemia.

A Phase II Trial of Ofatumumab In Subjects with Waldenstrom's Macroglobulinemia.

Development of virus-specific CD4(+) T cells during primary cytomegalovirus infection.

Although virus-specific CD4(+) T cells have been characterized extensively in latently infected individuals, it is unclear how these protective T-cell responses develop during primary virus infection in humans. Here, we analyzed the kinetics and characteristics of cytomegalovirus-specific (CMV-specific) CD4(+) T cells in the course of primary CMV infection in kidney transplant recipients. Our data reveal that, as the first sign of specific immunity, circulating CMV-specific CD4(+) T cells become detectable with a median of 7 days after first appearance of CMV-DNA in peripheral blood. These cells produce the T helper 1 type (Th1) cytokines IFNgamma and TNFalpha, but not the T helper 2 type (Th2) cytokine IL4. In primary CMV infection, the vast majority of these circulating virus-specific T cells have features of recently activated naive T cells in that they coexpress CD45RA and CD45R0 and appear to be in the cell cycle. In contrast, in people who have recovered from CMV infection earlier in life, virus-specific T cells do not cycle and express surface markers characteristic of memory T cells. After the initial rise, circulating virus-specific CD4(+) T cells decline rapidly. During this phase, a strong rise in IgM and IgG anti-CMV antibody titers occurs, concomitant with the reduction of CMV-DNA in the circulation.

Oral dosing of rats with OM-89 results in the appearance of specific OM-89 antibodies of the IgG 2a isotype: possible significance in the treatment of rheumatoid arthritis

OM-89 is a glycoprotein-rich extract of Escherichia coli shown to be effective in the treatment of rheumatoid arthritis (RA). It has been reported that oral dosing of animals results in the appearance of specific OM-89 antibodies. In the current study we have investigated some of the immunoglobulin isotypes that may be involved. OM-89 antibodies of IgG 1, IgG 2a and IgM isotypes were measured by ELISA in serum from rats dosed three times a week for 3 weeks at 4 or 40 mg kg −1. The results showed a small but significant rise in IgM and a greater rise in IgG 2a. The possibility that antigens within OM-89 (e.g. hsp65) may have homology with antigens involved in RA raises the possibility that OM-89 antibodies, particularly of the IgG 2 class, may block pathogenic antigens from being recognized by T cells.

Immunologic, endocrine and psychological influences on cortisol-induced immunoglobulin synthesis in vitro

In the present study, the relationship between psychological variables and hydrocortisone (HC)-induced immunoglobulin (Ig) production in vitro was investigated. Ninety-five human volunteers were selected based on their extreme (low or high) scores on a daily hassles and a symptoms questionnaire. Four groups were composed: (1) few hassles, few symptoms; (2) many hassles, few symptoms; (3) few hassles, many symptoms; and (4) many hassles, many symptoms. Incubating peripheral blood mononuclear cells (PBMC) for 2 weeks with HC (concentrations ranging from 10 −8 to 10 −6 M), resulted in a concentration-dependent rise in IgM and IgG secretion. In vitro IgM as well as IgG secretion were found to be related to plasma Ig levels. Plasma cortisol levels were positively associated with HC-induced IgG secretion. Furthermore, Ig secretion was found to depend on psychological profile, indicating a differential sensitivity of PBMC to HC for the four groups.

Immunological changes in normal pregnancy

During pregnancy the mother must tolerate intra-uterine allogenic fetal tissue. Failure of this tolerance may cause spontaneous abortion. The immunological changes occurring in normal pregnancy are poorly understood. The aim of this study was to investigate the immunological changes occurring in pregnancy. Thirty women in the first trimester; 10 in the second and 10 in the third trimester of pregnancy were studied and compared to age matched non-pregnant controls. In normal pregnancy there was an increase in the total white cell count with no change in the lymphocyte count. There was a fall in total T cell numbers and activated T cell numbers, with no change in helper/inducer or suppressor/ cytotoxic T cell numbers. [ 3H]Thymidine uptake in response to three different mitogens was increased. This implies an increase in potential for the cells to respond to mitogens. There was no change in interleukin-2 receptor levels, suggesting that despite this increased potential there was no general activation of the immune system. A rise in IgM and IgG was found after mitogen stimulation of peripheral blood lymphocytes, suggesting an increase in potential antibody production. These results demonstrate that lymphocytes from pregnant women have an increased potential rather than an increased activity.

Lung injury induced by short-term intermittent trimellitic anhydride (TMA) inhalation

We have developed a rat model of lung injury with interstitial pneumonitis, lung hemorrhage, and a systemic and pulmonary immune response to trimellitic anhydride (TMA)-haptenized proteins induced by TMA inhalation for 10 days. The present studies explored the induction of lung injury induced by short-term intermittent TMA inhalation, a model more likely to simulate short-term industrial exposures during inadvertent spills of TMA. Sprague-Dawley rats inhaled TMA powder (500 μg/m3) on days 1, 5, and 10, and were necropsied on day 30, 18 hours after a 6-hour TMA-inhalation challenge on day 29. Rats were bled every second day and at necropsy. Serum IgG, IgA, and IgM antibody to trimellityl rat serum albumin was measured by ELISA. There was a rise in IgM and IgA antibody to trimellityl rat serum albumin starting at day 5 that peaked at day 20 with a decline in IgM by day 30. IgG antibody rose at day 7, peaked at day 20, and plateaued. The IgG antibody level was 10 times higher than the IgA or IgM level. In a second experiment, 18 rats were administered TMA-inhalation exposure on days 1, 5, and 10, and a TMA challenge on day 22. The number of hemorrhagic foci, lung weights, and lung-displacement volumes at necropsy on day 23 were highly correlated with IgG, IgA, and IgM serum-antibody levels. In a final experiment, rats developed a mean of 112 hemorrhagic foci per lung on day 30 after receiving only two TMA-inhalation exposures on days 1 and 5 with a rechallenge on day 29. Short-term intermittent TMA-inhalation exposure can induce significant immunologic lung injury in this model.

Chlamydia, TWAR Strain Among Older Adults with Acute Pneumonia

The purpose of this study was to investigate the importance of Chlamydia, TWAR strain in acute pneumonia among older adults. In CY 1985, 197 patients admitted to the McClellan VAMC with community-acquired pneumonia (CAP) or who developed hospital-acquired pneumonia (HAP) were investigated extensively regarding microbial etiology, and only 94 yielded a defined agent. As part of this study, acute and 6-week convalescent sera from 45 patients were sent to Dr. J. T. Grayston (University of Washington, Seattle) to be tested for TWAR antibody. An additional 53 patients, mainly ≥65 years, with disease of unknown etiologies were studied in our laboratory for TWAR infection by modified microimmunofluorescence (MIF). Antigen dots for MIF slides were prepared from yolk sac homogenates for TWAR and C trachomatis, E strain. Sera were tested for IgM and IgG antibody by the indirect method. Criteria for a recent TWAR infection, as established by others, were; 4-fold rise in IgM or IgG titers; IgM titer of ≥32; or IgG titer ≥ 512. Of the total 98 patients tested, 10 were positive for TWAR. Nine of these had no other microbial etiology identified. Antibody titers were as follows: 4X rise in IgM and IgG, 1 patient (54 yr); IgM of ≥32, 2 patients (71, 47 yrs); IgM 32 and IgG 512, 1 patient (89 yr); IgG ≥512, 6 patients (81, 94, 74, 76, 37, 55 yr). The mean age of the 10 positive cases was 68. Six of the positive cases were >70 years and 3 of these were >80 years. Seven had CAP and 3 had HAP. One death occurred in the CAP group (age 74) and 2 deaths occurred in the HAP group (ages 71 and 55). The clinical features, routine laboratory findings, and chest radiographic findings were not distinctive, and instead were similar to other common causes of acute pneumonia. These data indicate that the new chlamydial TWAR agent may be an important cause of severe pneumonia among geriatric patients.

Total and Specific Immunoglobulin Response to Acute and Chronic Urinary Tract Infections in a Rat Model

Total and specific levels of immunoglobulins IgG, A and M were determined by an enzyme-linked immunosorbent assay (ELISA) in a rat model of urinary tract infections (cystitis) during the early and late phases of infection. The early response was characterized by rapid rise in IgM in serum and urine. This response decreased rapidly and was undetectable in urine after eight weeks. Correlation between total serum and urine levels of IgM was not found although a chronological relationship was observed. Total and specific serum and urine IgA responses were erratic. Concentrations of IgA were low and this antibody class was undetectable in urine until the infection had been established for six weeks. In contrast, total serum and urine IgG increased in concentration at five days post infection and reached total maximum by weeks four to eight, then declined, but remained detectable over 24 weeks. Specific IgG titers remained elevated in serum but declined in urine between four and 10 weeks. A correlation between total serum and total urine IgG was found. Also, bacteria generated a concomitant nonspecific response, a part of which was detected against a common antigen expressed on E. coli J5 strain that cross-reacts with a number of gram negative genera. The results show that IgM chronologically is the first antibody to appear in increased amounts in the serum and urine, followed by IgG. The data also suggests a relationship exists between total serum IgG and total urine IgG which may affect the host’s ability to eliminate urinary infection.

Anti-Plasmodium falciparum antibodies acquired by residents in a holoendemic area of Liberia during development of clinical immunity.

Sera from 48 children and adolescents (2-15 years of age), residing in a malaria holoendemic area of Liberia were investigated for specificities and isotypes of anti-P. falciparum antibodies. No clear-cut relationship to the development of clinical immunity was found when the overall antibody activities to total parasite antigens were determined by enzyme-linked immunosorbent assay (ELISA). Although there was a certain rise of IgM, total IgG- and IgG2 antibody activities, this was most pronounced at ages when a clinical but nonsterile immunity is already present. When the sera were investigated by immunoprecipitation of 35S-methionine labeled parasite polypeptides, the total number of parasite antigens precipitated was similar at all ages. Analysis by indirect immunofluorescence (IFA), registering antibodies to intracellular parasite antigens, revealed no age-dependent changes in antibody titers. In contrast, when the sera were assayed by a novel IFA, specific for a restricted number of parasite antigens in the membrane of infected erythrocytes, the frequency of positive sera as well as the anti-P. falciparum titers rose in parallel with the development of clinical immunity. Thus, these antigens appeared to be important inducers of protective immune responses and may be suitable candidates for a vaccine against the asexual blood stages of P. falciparum.

II. Multicentre clinical trial of diets for low birthweight infants: interim analysis of short term clinical and biochemical effects of diet

In 3 of 5 collaborating centres, two clinical trials comparisons are being made between infants randomly assigned to a preterm formula (PTF) or banked milk (BBM) fed as sole diets or in conjunction with maternal milk. (n=200 at second interim analysis). BBM fed infants showed: 1. increased incidence of: severe hyponatraemia (Na <126 mmol/1, p <0.05), radiological and biochemical evidence of rickets of prematurity (hypophosphataemia and higher alkaline phosphatase p <0.01) and riboflavin deficiency (erythrocyte glutathione reductase activation coefficient >1.3, p<0.01); 2. higher peak plasma bilirubin and more prolonged hyperbilirubinaemia (p<0.01), 3. higher plasma prolactin and growth hormone concentration (p<0.01). PTF fed infants showed 1. increased: growth rates (reported elsewhere), gastric pooling (p<0.01) and latent systemic anaphylactic sensitisation to cows milk (basophil histamine release to cowsmilk and anti IgE challenge, p<0.01); 2. faster postnatal fall in plasma IgG and rise in IgM (p<0.05); 3. lower plasma calcium (week 1) and potassium (p<0.02) 4. higher platelet count (p<0.05) and plasma concentration of some amino acids, notably threonine (p<0.0001). We conclude that patterns of short term response to diet are complex and cannot be used to predict an overall clinical benefit of a feeding regime - their clinical significance can be assessed only by follow up studies, the principle concern of these trials.

Thymostimulin therapy in melanoma patients: Correlation of immunologic effects with clinical course

Thirty-two nonmetastatic melanoma patients with low T-lymphocyte values were treated with a thymic extract, thymostimulin (TS) (8 patients), DTIC (8 patients), or surgery alone (16 patients). In the 8 patients receiving TS, active E-rosette (T-Ea) and total E-rosette (T-Et) counts rose to normal levels and there was a significant rise in IgM and IgD receptors. Six out of eight patients treated with TS showed no evidence of metastases after 34 months, while 7 8 patients on DTIC and 13 16 patients on surgery alone developed metastases. Twenty metastatic patients with low T-lymphocyte values received either DTIC plus TS or DTIC alone. Total lymphocyte, T-Ea, and T-Et counts did not increase in either group nor was there a significant difference between the group on DTIC plus TS and the group on DTIC alone. The survival rate of patients on DTIC plus TS did not differ significantly from that on DTIC alone.

Microbiology and pathogenesis of acute salpingitis as determined by laparoscopy: What is the appropriate site to sample?

Acute salpingitis is a polymicrobial disease. Neisseria gonorrhoeae and anaerobic gram-positive cocci were the predominant microorganisms isolated from the fallopian tubes of salpingitis patients. Gonococci were isolated from the fallopian tubes in eight of 35 (23%) patients; anaerobic bacteria were recovered from 10 of 35 (28.5%). Although Chlamydia trachomatis was not recovered from the fallopian tube exudate, there was abundant serologic evidence of chlamydial infection in the salpingitis patients. Twenty-three percent of patients with paired sera had a fourfold rise in IgM and IgG titer, which was consistent with systemic chlamydial infection. Comparison of cultures obtained via laparoscopy and culdocentesis suggested that culdocentesis is not an accurate reflection of the microbial milieu in the fallopian tube.

Trypanosomes

Most immunological studies on trypanosomes have been made on species in the subgenus Trypanozoon which includes those causing sleeping sickness in man, but members of the subgenera Duttonella and Nannomonas are more important as the cause of disease in cattle. Wherever possible, studies on these subgenera in cattle are discussed in this paper. The antigenic structure of trypanosomes is complex and common antigens between species, strains and populations occur in homogenates. Antigens variation is responsible for trypanosome surface alter during infection and this antigenic variation is responsible for many of the immunological problems of trypanosmiasis. The characteristics humoral response to infection is a rapid and sustained rise in IgM followed by a later increase in IgG but little is known about cell-mediated immunity in trypanosomiasis. The altered immunoligical state of the infected animal may be of significance in the pathogenesis of the disease in which anemia is marked and kinin production occurs. Possible methods of stimulating protective immunity are discussed and the suppression of immune response to other antigens is analysed.

Immune response in human subjects at high altitude.

Levels of immunoglobulins were determined in persons exposed to high altitude. The individuals studied included high altitude natives, sea level residents at high altitude for 2 years, and recent arrivals at high altitude. Increased IgG and IgA levels were found in high altitude natives and sea level residents at high altitude for 2 years when compared with sea level residents. In recent arrivals marked increase of IgG and IgG levels and slight rise in IgM was seen. Recent arrivals who suffered from high altitude pulmonary oedema showed marked elevation of IgG, IgM, and IgA. Immunoglobulin responses to both primary and secondary TAB inoculation were of a higher magnitude and more sustained at high altitude than at sea level.

Les taux seriques d'immunoglobulines chez l'enfant Africain: Variations saisonnieres et facteurs ethniques

The blood titers of IgG, IgA and IgM and total proteins were determined m October 1971 (dry season) and again in April 1972 (wet season) among girls and boys belonging to 4 ethnic groups: White, Bantu, Indian, Mixed. Parasitic studies were also done. These studies indicate a rise of IgM among the girls and of IgA in both sexes from October 1971 to April 1972. The average IgM titer among the four groups is higher than the one found in the Occident. This is especially notable for the Bantu and the Mixed. The Indian levels exceeded, on the average, the White group's. The average IgG figures are only slightly higher than those found in the literature for Western populations. Genetic influences do not appear to explain the differences found between the ethnic groups. The role of environment is stressed, and parasitic influences are discussed.

Some Serum Globulin Changes in East Coast Fever

Using single radial immunodiffusion tests, changes in concentrations of IgG 1 , IgG 2 , IgM and a protein designated 7Sγ 1 were measured in the sera of cattle undergoing mild, severe and fatal reactions to experimental East Coast fever (Theileria parva infection). In cattle dying of East Coast fever there was a profound fall in IgM and 7 S γ 1 levels after establishment of T. parva in the peripheral lymph nodes; IgG 1 levels also fell, but not IgG 2 . In cattle that recovered from severe infections there was a marked drop in the levels of all 3 immunoglobulins and in 7 Sγ 1 , but not until the peak of the clinical reactions. In these cattle the levels ofIgG 1 , IgG 2 and IgM returned to the pre-infection levels within 5 days and of 7 Sγ 1 within 14 days. However, the IgG 1 and, in particular, IgM levels continued to rise after recovery from infection, reaching a peak concentration by day 28 post-infection and thereafter falling slowly to pre-injection levels. In cattle recovering from mild infections there were negligible effects on IgG 1 and IgG 2 levels, but a rise in IgM and a slight fall in 7 Sγ 1 levels were detected.

The detection of a silent coxsackie B-5 virus perinatal infection

Summary Perinatal infection was detected in a normal newborn infant whose mother developed pleurodynia 6 days before delivery. Coxsackie B-5 virus was recovered from the mother but not from the infant, whose infection was demonstrated only by measuring specific neutralizing antibody content in immunoglobulin fractions in sequential serum specimens. A rise in IgM (19S) globulins containing specific antibody occurred between 4 and 14 days of age, but by the time the infant was 8 months old, no antibody to Coxsackie B-5 could be demonstrated, indicating that the infection was probably a modified one which did not result in durable immunity.