Studies of human peripheral lymph. II. Low lymphocyte count and few B-lymphocytes in peripheral lymph of patients with chronic lymphocytic leukaemia.
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Adult↗
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Prognostic value of single measurements of beta-2-microglobulin, immunoglobulin A in HIV disease after controlling for CD4 lymphocyte counts and plasma HIV RNA levels.
The interrelationships between the CD4 lymphocyte count, plasma viral load [human immunodeficiency virus (HIV) RNA], beta-2-microglobulin (beta2-M) and immunoglobulin A (IgA) and the mortality risk was explored in 234 HIV-infected individuals (median CD4 count 230 cells/mm3, range 1-1,247). Product-moment correlation analysis was used to study the association between beta2-M, IgA and HIV RNA. A proportional hazards Cox model was used to estimate the relative hazard (RH) of death. Both beta2-M (r = 0.49, p < 0.0001) and IgA (r = 0.42, p < 0.0001) were positively correlated with HIV RNA. High beta2-M levels were associated with an increased risk of death in both univariate Cox analysis and after adjustment for HIV RNA, CD4 lymphocyte count and age [RH = 1.16 per 100 nmol/l higher beta2-M, 95% confidence interval (CI) 1.05-1.27]. Raised IgA levels were associated with shorter survival in individuals with a CD4 count above 50 cells/mm3 in univariate analysis as well as after adjusting for age and CD4 lymphocyte count (RH = 1.19 per 10 micromol/l higher IgA, 95% CI 1.01-1.39). However, this association was no longer significant after further adjusting for HIV RNA. In conclusion, beta2-M levels provided additional prognostic information for survival to the information obtained by CD4 count and HIV RNA levels, whereas serum IgA only was a weak prognostic marker in this fairly progressed cohort.
Adult↗
Declining lymphocyte counts following cytomegalovirus (CMV) infection are associated with fatal CMV disease in bone marrow transplant patients.
A previous pilot study conducted on 12 bone marrow transplant recipients suggested that detection of cytomegalovirus (CMV) in lymphocytes was associated with a drop in lymphocyte counts and death due to CMV disease. To test the association between decreasing lymphocytes and CMV-related death, we undertook a retrospective study of 332 CMV-infected patients transplanted between 1987 and 1990. The patients were divided into three groups: I = 170 patients who survived their infection and were alive at the time of the study; II = 103 patients who died of causes other than CMV infection; and III = 59 patients who died of CMV disease. Lymphocyte counts were analyzed during a 24-day period, starting 10 days before the day of first positive CMV culture (day 0). Lymphocyte counts were significantly lower in Group III from day 0 through day +14 (p < .001 vs. group I; and p = .002 vs. group II). Multivariate statistical analysis was used to adjust for other differences between the groups that might influence lymphocyte numbers. Average lymphocyte counts in patients who died of CMV disease decreased by an average of 35% after day 0. The differences in lymphocyte counts remained independent of the effects of acute graft-vs.-host disease (GVHD), time since transplant, transplant type, and high-dose steroid treatment. In summary, these data suggest that in some patients a drop in lymphocyte counts is a consequence of CMV infection associated with fatal CMV disease. Whether this can be attributed to direct infection of lymphocytes, a defective immune response, or some other mechanism remains to be determined.
Adult↗
Changes in plasma HIV RNA levels and CD4+ lymphocyte counts predict both response to antiretroviral therapy and therapeutic failure. VA Cooperative Study Group on AIDS.
BACKGROUND: Markers are needed for assessing response to antiretroviral therapy over time. The CD4+ lymphocyte count is one such surrogate, but it is relatively weak. OBJECTIVE: To assess the association of changes in plasma human immunodeficiency virus (HIV) RNA level and CD4+ lymphocyte count with progression to the acquired immunodeficiency syndrome (AIDS). DESIGN: Analysis of data from a subset of patients in a multicenter, randomized, clinical trial. SETTING: Six Veterans Affairs medical centers and one U.S. Army medical center. PATIENTS: 270 symptomatic HIV-infected patients from the Veterans Affairs Cooperative Study on AIDS. INTERVENTION: Patients were randomly assigned to receive zidovudine or placebo initially; a cross-over protocol was established for patients receiving placebo who had disease progression. MEASUREMENTS: Reverse transcriptase polymerase chain reaction on cryopreserved plasma samples, previously obtained CD4+ lymphocyte counts, and clinical events. RESULTS: For each decrease of 0.5 log10 copies/mL in plasma HIV RNA level, averaged over the 6 months after randomization, the relative risk (RR) for progression to AIDS was 0.67 (P < 0.001). In a subset of 70 treated patients with long-term follow-up, a return to baseline plasma HIV RNA levels within 6 months of randomization was associated with progression to AIDS (RR, 4.28; P = 0.004). Plasma HIV RNA levels or CD4+ lymphocyte counts over time were more strongly associated with progression to AIDS than were baseline levels or counts. CONCLUSIONS: An adequate virologic response after initiation of antiretroviral therapy seems to require a decrease in plasma HIV RNA level of at least 0.5 log10 copies/mL that is sustained for at least 6 months. The independent relation between plasma HIV RNA level and CD4+ lymphocyte count over time and clinical outcome suggests that the measurement of plasma HIV RNA level, in addition to the CD4+ lymphocyte count, has a role in guiding the management of antiretroviral therapy.
Acquired Immunodeficiency Syndrome↗
Administration of ATG according to the absolute T lymphocyte count during therapy for steroid-resistant rejection.
In renal transplantation, treatment of steroid-resistant rejection (SRR) with antithymocyte globulin (ATG) has been widely reported but over-immunosuppression remains a common problem. In the first ten patients (group 1) treated for SRR with rabbit ATG, three developed serious viral infections and two deaths occurred due to CMV pneumonitis. ATG was only omitted if thrombocytopenia or neutropenia occurred. In the next 17 patients (group 2) with SRR, ATG was administered according to the absolute T lymphocyte count. T lymphocytes were measured by flow cytometric analysis of CD3-labelled lymphocytes. ATG dosage was adjusted on a daily basis to keep the absolute T lymphocyte count under 50 cells/microliters. Administration of ATG according to the absolute T lymphocyte count resulted in a significant reduction in the mean dose of ATG given to the group 2 patients (P < 0.001). A significant decrease in the incidence of serious viral infections (P = 0.04) was achieved without reducing the ability of ATG to reverse the SRR (P = 0.29) or increasing the number of grafts lost at 1 year in the group 2 patients (P = 0.23).
Adult↗
Predictive value of repeated measurements of CD4 lymphocyte counts on progression to AIDS.
OBJECTIVE: Description of the relationship between repeated measurements of CD4 lymphocyte count and development of AIDS in asymptomatic HIV-infected patients. DESIGN: Repeated measurements of CD4 lymphocyte counts over an AIDS-free period in asymptomatic HIV-infected patients, and follow-up of the cohort to record subsequent clinical progression to AIDS. METHODS: The cohort was studied in a double-blind randomized clinical trial. CD4 lymphocyte counts were measured on three occasions over 8 months in 851 patients. RESULTS: Eighty subsequent clinical progressions to AIDS were recorded during a median follow-up period of 15.3 months. Each of the three measurements of CD4 lymphocyte count were separately predictive of subsequent progression to AIDS. However, when the three measurements were included simultaneously in a predictive model only the last measurement showed a significant predictive value. Change in individual CD4 count was also related to the risk of developing AIDS, but was no longer significant when the most recent measurement was included in the model. CONCLUSION: These results indicate the closeness of the relationship between the actual state of the immune system and subsequent progression to AIDS.
Acquired Immunodeficiency Syndrome↗
Prognostic value of pre-treatment lymphocyte count and T cell levels in localized bronchogenic carcinoma.
In the patient with clinically localized bronchogenic carcinoma, the pre-treatment peripheral blood lymphocyte count and the thymus-dependent lymphocyte (T cell) level correlated with the prognosis of the tumor histology was either squamous cell, oat cell, or undifferentiated carcinoma. Patients whose pre-treatment lymphocyte count was less than 1,000/ml or whose T cell level was less than 750/ml either died or developed distant metastases by nine months after treatment of their localized tumor. By contrast, 55% of patients whose pre-treatment T cell level was greater than 750/ml were alive and without evidence of metastases nine months after treatment (P less than 0.02). Analysis of survival of these patients by the life-table method through the first post-treatment year further demonstrates the prognostic value of a low pre-treatment lymphocyte count or T cell level. The pre-treatment lymphocyte count and T cell level in patients with adenocarcinoma did not correlate with prognosis.
Adult↗
Prognostic value of bronchoalveolar lavage lymphocyte count in recently diagnosed pulmonary sarcoidosis.
We prospectively looked at the prognostic value of bronchoalveolar lavage (BAL) lymphocyte count in 98 patients with recently diagnosed (less than 4 months) untreated sarcoidosis. These 50 men and 48 women (mean age, 37.4) were followed up for a period of 6 to 60 months (mean, 25.6), and were clinically evaluated every three to six months with repeated chest roentgenograms and pulmonary function tests. Twenty-four patients required steroid treatment during the study period. The proportion of treated patients was not significantly higher in the group presenting a BAL lymphocyte count less than or equal to 30 percent at diagnosis than in the group with fewer lymphocytes (31.9 and 17.7 percent of total group respectively, p = 0.10). No significant change in TLC, FRC, FVC, FEV1 or DLCO was found at follow-up between the groups with or without an initial high lymphocyte count. In the treated group, BAL lymphocyte percent weakly correlated with the improvement of FEV1 and FVC while on steroid treatment (mean duration: 3.5 months): r = 0.41, p = 0.031 and r = 0.36, p = 0.05 respectively; no correlation was found with lung volumes and DCO. We conclude that BAL lymphocyte count at the time of diagnosis is not a helpful predictor of lung function deterioration in recently diagnosed sarcoidosis and is not very useful in predicting response to treatment.
Adult↗
Improvement of the predictive value of CD4+ lymphocyte count by beta 2-microglobulin, immunoglobulin A and erythrocyte sedimentation rate. The Multicentre Cohort Study Group.
OBJECTIVE: To evaluate whether the use of immunological markers in addition to CD4+ lymphocyte count can improve the prediction of the probability of developing AIDS within a given period. DESIGN AND SETTING: Prospective multicentre cohort study of homosexual men. PATIENTS: A total of 447 HIV-positive homosexual men followed prospectively at 6-month intervals (median time of observation, 47 months). METHODS: Estimation of AIDS-free time using lifetable plots by Cutler and Ederer and Weibull parametric models. A stepwise multivariate regression analysis was used to calculate the optimal combination of the parameters studied. RESULTS: In general CD4+ lymphocyte counts are most important for the prediction of AIDS-free time. The use of serum levels of beta 2-microglobulin (beta 2M), immunoglobulin A (IgA) and erythrocyte sedimentation rate (ESR) can significantly improve the predictive value of CD4+ lymphocyte counts. However, the usefulness of these parameters depends on the stage of HIV disease. In patients with a CD4+ lymphocyte count > 500 x 10(6)/l, only IgA level had a significant predictive value; none of the other parameters significantly improved the model. In patients with a CD4+ lymphocyte count < 500 x 10(6)/l, the absolute number of CD4+ cells itself was the most important single predictive parameter, but the prediction of AIDS was significantly improved by the addition of the other parameters investigated. The most powerful combination of parameters in this group was CD4+ count, beta 2M and ESR. CONCLUSION: Determination of serum IgA, beta 2M and ESR in addition to CD4+ lymphocyte count may aid the choice of specific therapeutic regimens or systems of care for HIV-positive individuals.
Acquired Immunodeficiency Syndrome↗
Left ventricular dysfunction is associated with CD4 lymphocyte count rather than opportunistic infection in human immunodeficiency virus infection.
BACKGROUND AND PURPOSE: Left ventricular (LV) dysfunction is often found in the early stage of human immunodeficiency virus (HIV) infection and deteriorates with disease progression. CD4 lymphocyte count and opportunistic infection are the major indicators for the clinical staging of HIV infection. This study investigated the association of these indicators with LV dysfunction in the clinical course of HIV infection. METHODS: HIV-positive patients without cardiac manifestations consecutively admitted from May 1998 to April 1999 were enrolled in the study. Echocardiographic LV function evaluation and measurement of CD4 lymphocyte count were performed. Parameters for LV systolic and diastolic functions were compared between patients with CD4 lymphocyte count >or= 200/microL and those with CD4 < 200/microL. In patients with CD4 < 200/microL, LV function was further correlated with the presence or absence of opportunistic infections. RESULTS: Ninety eight HIV-positive patients including 52 with CD4 >or= 200/microL and 46 with CD4 < 200/microL were studied. One half of the 46 patients with CD4 < 200/microL had active opportunistic infections. We found that LV fractional shortening, ejection fraction, and isovolumic relaxation time were all significantly lower in the patients with CD4 < 200/microL compared with those with CD4 >or= 200/microL. Moreover, these LV systolic and diastolic dysfunctions were positively correlated with decreased CD4 lymphocyte count. In contrast, no difference was found in these parameters between patients with and without opportunistic infections. In multiple regression analysis, CD4 lymphocyte count was found to be the only factor for predicting the LV systolic and diastolic dysfunction. CONCLUSIONS: Both LV systolic and diastolic function deteriorate as the CD4 lymphocyte count decreases in HIV infection. Opportunistic infection seems to have a limited role in the pathogenesis of LV dysfunction in advanced HIV infection.
AIDS-Related Opportunistic Infections↗
Effect of aging on the peripheral blood lymphocyte count.
Analysis of 1684 inpatient and 884 outpatient peripheral blood counts revealed the following: (1) The absolute lymphocyte count declines sharply from 5000/microletre to 2000/microletre in the first two decades, remains constant for three decades, then declines at an accelerated rate beginning in the 40s, to reach 1500/microletre at age 90. (2) The absolute granulocyte count does not show age-dependent variation, remaining essentially constant throughout life. (3) The values of absolute lymphocytes are indistinguishable for ambulatory or hospitalized subjects except for higher absolute lymphocyte counts in hospitalized children in the first decade. (4) The data support other evidence for declining cellular and humoral immunity in aging man.
Adolescent↗
Characterization of circulating T-lymphocyte subsets in alcoholic liver disease by monoclonal antibodies: correlation with the absolute lymphocyte count.
Peripheral blood T-lymphocytes from 27 patients with alcoholic liver disease were assessed on the basis of their ability to react with OKT monoclonal antibodies. A significant positive correlation was observed between the absolute numbers of T-lymphocytes and suppressor/cytotoxic T cells and the absolute lymphocyte count. These data suggest that quantitative changes in T-lymphocyte subsets in alcoholic liver disease do not necessarily reflect an imbalance in T immunoregulatory mechanisms.
Antibodies, Monoclonal↗
Modeling of the change in CD4 lymphocyte counts in patients before and after administration of the human immunodeficiency virus protease inhibitor indinavir.
We investigated the relationships between changes in CD4 lymphocytes counts over 24 weeks after the initiation of therapy with indinavir at dosages of > or = 2.4 g/day (n = 15) in human immunodeficiency virus-positive patients and compared them to the baseline values. Starting CD4 count were linked to the time-weighted average CD4 cell count (return) through a nonlinear effect model. The diminution of destruction of CD4 cells after the initiation of indinavir therapy was estimated by fitting simultaneous differential equations to the data by using a linked lymph node (LN)-blood (BL) (two-compartment) system in which there is a constant rate of generation (R), first-order transfer rate constants (KLN-BL and KBL-LN) of compartment exchange, and first-order rate constants of CD4 destruction in the absence and presence of indinavir (KLN-OUT1 and KLN-OUT2). The half-life of CD4 lymphocytes was calculated from the rate constants by standard two-compartment methods. The CD4 lymphocyte counts at the start and return were linked in a sigmoid-Emax model were the maximal effect (Emax) was at 574.6 cells/microliters and 50% of the effect occurred at 157.1 cells/microliters (r2 = 0.94; P < 0.001). The mean +/- standard deviation (median) KLN-OUT2 was 0.574 +/- 0.202 (0.589), indicating that indinavir decrease the destruction of CD4 cells by circa 41 to 42%. The mean (median) CD4 half-life was 11.5 +/- 5.72 day (10.3 days). In multivariate analysis, KLN-OUT2 was significantly correlated with starting the CD4 cells count and the change in the CD4 cell count on therapy. The relationship between CD4 lymphocyte half-life and the starting CD4 lymphocyte count was hyperbolic, with a rapid increase in half-life as the CD4 count decreased. On the basis of the calculated half-life, the average production (destruction) of CD4 lymphocytes was approximately 3 x 10(9) cells/day, with an individual variation of 44-fold. These findings suggest that (i) the CD4 lymphocyte cell count at the start is significantly correlated to both the decrease in the destruction rate of CD4 cells and the degree of change in the CD4 lymphocytes on therapy, (ii) the lower the initial CD4 lymphocyte count, the higher the amount of CD4 lymphocyte turnover and the lower the ability of the immune system to increase absolute CD4 lymphocyte levels after viral suppression, consistent with a decreased regenerative capacity with progression of disease; and (iii) the increase in CD4 lymphocytes is likely secondary to the expansion of proliferating pool of cells since our determinations are based on 24 weeks of effect.
Anti-HIV Agents↗
Corticosteroid treatment in pulmonary sarcoidosis: do serial lavage lymphocyte counts, serum angiotensin converting enzyme measurements, and gallium-67 scans help management?
Thirty two patients with persisting pulmonary sarcoidosis fulfilling defined criteria for treatment were managed according to a standard clinical protocol. In this an attempt was made to achieve and maintain maximal radiographic and physiological improvement with individually titrated doses of corticosteroids. Lavage cell counts, serum angiotensin converting enzyme (SACE) determinations, and gallium-67 scans were planned at standard intervals but were not used in management decisions. The study analysed serial measurements in relation to changes in the clinical measurements. Twelve patients' radiographs showed complete clearing, seven cleared partially, and 13 had partial clearing with evidence of fibrosis. There was no predictive value in the initial lavage lymphocyte counts or the SACE or gallium measurements. Notably, in seven patients, substantial radiographic improvement was observed when the initial lavage lymphocyte counts were normal. Higher initial lavage neutrophil counts (p less than 0.02), higher initial radiographic profusion scores (p less than 0.02), and lower vital capacity (p less than 0.01) and carbon monoxide transfer factor (p less than 0.05) were related to incomplete clearing. A repeat study of the patients when their radiograph had cleared maximally showed that the levels of lavage lymphocytes, SACE, and gallium tended to fall, but frequently remained raised even in the presence of a normal radiograph or vital capacity or both. On the other hand, however, most of the patients with a normal lavage lymphocyte count showed persisting abnormality of the radiograph, lung function measurements, SACE, and gallium scan (or of at least one of these indices). The interrelationships between changes in clinical indices (radiograph, vital capacity, and transfer factor) and in lavage lymphocyte counts, SACE, and gallium scans showed that concordance was fairly poor in each comparison; lavage lymphocytes showed a greater major discordance than did the other pairs of measurements. Symptom free patients with normal or stable radiographic appearances have been followed for many months and have shown no clinical deterioration despite abnormal lavage lymphocyte counts, SACE, and gallium scans. Radiographic relapse, within the criteria defined, was seen in only four patients during the study; this was reflected in the gallium counts in three and in SACE and lavage lymphocyte counts measurements in two. It is concluded that serial lavage lymphocyte counts, serum angiotensin converting enzyme measurements, and gallium-67 scans are not consistently more sensitive methods by which to monitor patients with sarcoidosis during treatment than are serial measurements of high quality radiographs and results of standard lung function tests.
Adult↗
[Clinical value of the blood lymphocyte count in thoracic sarcoidosis in adults. Apropos of 123 cases].
Lymphocyte counts in the peripheral blood were performed in 123 patients with thoracic sarcoidosis and in 33 healthy subjects. A significant decrease in the number of lymphocytes as compared to controls was observed, at least in patients of Caucasian origin. This lymphopenia was more pronounced when the disease was of more than 10 years' duration, was accompanied by extrathoracic manifestations and belonged to radiological groups II or III. The only parameter of pathological activity with which it correlated was serum angiotensin converting enzyme activity. Patients from the french Caribbean had scattered lymphocyte counts which precluded any firms conclusion.
Adult↗
Association of asymptomatic oral candidal carriage, oral candidiasis and CD4 lymphocyte count in HIV-positive patients in China.
OBJECTIVES: To compare the prevalence of asymptomatic oral candidal carriage in healthy volunteers with human immunodeficiency virus (HIV)-positive patients in China, as well as to investigate the relationship between CD4+ lymphocyte count and oral candidal colonization or oral candidiasis. METHODS: Oral candidal carriage and oral candidiasis were investigated in 101 patients with HIV-infection seen at Youan Hospital, Beijing, China. Two hundred and seventeen healthy volunteers were involved as a control. Culture from saliva was used to test for the presence of oral Candida. CD4+ lymphocyte count was measured by flow cytometry. All data were analyzed statistically by SAS. RESULTS: Asymptomatic oral candidal carriage rate (28.6%) in HIV-positive group was similar to that in the healthy group (18.0%; P = 0.07). No significant difference in CD4+ lymphocyte count was found between oral Candida carriers and non-carriers among HIV-positive subjects (P = 0.89). However, the frequency of oral candidiasis increased with the decrease in CD4+ lymphocyte count (P < 0.0001), and pseudomembranous candidiasis was predominant in HIV-positive patients with CD4+ <200 cells microl(-1) (66.7%). CONCLUSIONS: In HIV-positive subjects, asymptomatic oral candidal colonization is not related to CD4+ lymphocyte count of blood, and the carriage rate is similar to that in the healthy population. Oral candidiasis is more likely to be observed in HIV-positive patients who have a low CD4+ lymphocyte count.
Adult↗
Total lymphocyte counts in adult HIV/AIDS patients in Port Moresby General Hospital.
We carried out a prospective study of total lymphocyte counts in 124 adult patients who were diagnosed with HIV (human immunodeficiency virus) infection and/or AIDS (acquired immune deficiency syndrome) and were admitted to Port Moresby General Hospital (PMGH) from January to June 2003. The median and mean values of lymphocyte counts in these patients were found to be 0.7 x 10(9)/l and 0.9 x 10(9)/l, respectively, with a standard deviation of 0.7, both of which counts are significantly lower (p < 0.0001) than those found in members of a control population who were well and HIV-antibody-negative. We found that the lower the total lymphocyte count, the more clinically advanced was the HIV disease state. Haemoglobin values were also significantly lower in these patients. For 35% of these patients, tuberculosis was the principal diagnosis made upon being admitted. An apparent 11% of the patients who had a clinical suspicion of AIDS were HIV-antibody-negative. Total lymphocyte count methods could be used in developing countries that do not have appropriate facilities for CD4 count and viral load assays in order to monitor the patient's disease state and progression towards AIDS.
Adolescent↗
The relative prognostic value of plasma HIV RNA levels and CD4 lymphocyte counts in advanced HIV infection.
OBJECTIVE: It has been suggested that the plasma HIV RNA level is a better predictor of AIDS and death than the CD4 lymphocyte count. We assessed whether the prognostic value of plasma virus levels was different according to the CD4 count. DESIGN: Prospective cohort study of HIV-infected patients followed for a median of 2.91 years (range, 0.02-4.54). SETTING: Department of Infectious Diseases at Rigshospitalet, Copenhagen, Denmark. PARTICIPANTS: A group of 255 HIV-infected individuals with an initial measurement of CD4 lymphocyte count and plasma HIV RNA. MAIN OUTCOME MEASURE: Survival time. RESULTS: The plasma HIV RNA (median 101410 copies/ml; range (range 200-7200000) and the CD4 lymphocyte count (median 250 cells x 10(6)/l; range 1-1247) were negatively correlated (Pearson r = -0.53; P < 0.00001). Of the 255 patients, 110 died during follow-up. Overall, a higher HIV RNA level was associated with increased risk of death, but the association was smaller in patients with lower CD4 lymphocyte counts (test for interaction P < 0.0001). In patients with CD4 count below 50 cells x 10(6)/l the association between HIV RNA and risk of death was not statistically significant (relative hazard per 10-fold higher HIV RNA level was 1.53; P = 0.11; adjusted for age and CD4 count) while that between the CD4 count and risk of death was highly significant (relative hazard per 50% lower CD4 count 1.38; P = 0.005; adjusted for age and HIV RNA level). CONCLUSIONS: Patients were relatively lightly treated with antiretroviral drugs both before and during this study. In this situation, it appears that the HIV RNA level has a relatively weak association with risk of death in patients with advanced HIV infection and that the CD4 lymphocyte count is probably more useful in assessing prognosis.
Adult↗