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Plasmapheresis and cold sensitivity of immunoglobulin molecules. II. A study of macroglobulinemia polyclonalis spuria and immune complex disease.

The indications for plasmapheresis in the different hyperviscosity syndromes are discussed on the basis of data on relative serum viscosity at 13 and 37 degrees C. Beside monoclonal macroglobulinemia there are conditions with a high content of polyclonal IgM and also of IgG and IgA where hyperviscosity is a dominant symptom. The importance of what may be called macroglobulinemia polyclonalis spuria is stated and a number of patients belonging to this type are discussed. Polyclonal increase in IgG, even at high levels, usually does not cause severe hyperviscosity. Case histories of patients with rheumatoid disease and marked hyperviscosity constitute one group. Another is formed by diseases leading to the development of immune complexes. Such complexes are usually caused by binding of polyclonal IgG to monoclonal IgM, but other combinations are also known. A number of clinical examples of these different disease conditions, some probably indicating intense plasmapheresis, are analyzed. The limited value of plasmapheresis alone without cytostatic treatment is stressed as regards hyperviscosity. Another indication is removal of noxious protein components.

Aged↗

Warm autoimmune hemolytic anemia is an IgM-IgG immune complex disease.

Warm autoimmune hemolytic anemia (WAIHA) is characterized by polyclonal IgG autoantibodies binding to red blood cells (RBC). The characterization of the autoantigen in WAIHA has not yet led to definitive results, and the etiology of RBC autoantibodies remains unclear. An altered control of self-reactive IgG by autologous IgM has been proposed as the underlying mechanism of disease in WAIHA, suggesting that IgM-IgG immune complexes contribute to the pathophysiology of the disease. In the present study, we purified and characterized IgM from plasma of WAIHA patients and from healthy controls using FPLC-based protocols and optical biosensor technology, and investigated IgG present within the IgM fractions. We provide evidence that IgM-IgG immune complexes in plasma and associated with the RBC membrane are the characteristic feature of WAIHA, independent of the etiology of the disease. IgM-IgG immune complexes of WAIHA patients differ from IgM-IgG immune complexes of healthy individuals with regard to quantity and to structural composition. The data suggest that self-immunoglobulin is the original autoantigen underlying WAIHA. The molecular characterization of IgM-IgG immune complexes may define new targets for therapeutic intervention in WAIHA.

Adult↗

Potential association between calcified thoracic lymphadenopathy due to previous Histoplasma capsulatum infection and pulmonary Mycobacterium avium complex disease.

BACKGROUND: Among patients with pulmonary disease due to Mycobacterium avium complex (MAC) seen recently at our center, a substantial number have had extensive calcified mediastinal, hilar, and peribronchial lymphadenopathy, a finding historically inconsistent with pulmonary MAC disease. METHOD: We retrospectively studied the frequency of calcified lymphadenopathy in the chest and prevalence of known risk factors for MAC infection in 79 patients with pulmonary MAC disease who were referred to our hospital over a 1-year period. RESULTS: Calcified intrathoracic adenopathy was present in 25 of the 79 patients (32%). Residential histories revealed that 20 of the 25 patients (80%) with such calcified chest adenopathy reported living for substantial periods in the regions indigenous for Histoplasma capsulatum. In contrast, the residences of patients without calcified chest adenopathy were more evenly distributed throughout the country. Nineteen of these 25 patients (76%) with calcified chest adenopathy had no known predisposing risk factor for the infection; in contrast, the proportion of patients with no calcified adenopathy who also had no identifiable classic risk factor tended to be lower (32/54, 59%). CONCLUSION: In this retrospective study, we observed that (1) a large number of patients with pulmonary MAC disease had no identifiable risk factor, (2) calcified chest adenopathy was present in one third of the patients, (3) the residential history of those with calcified adenopathy mirrored the endemic region of histoplasmosis, and, (4) conversely, those patients with pulmonary MAC who lived outside the histoplasmosis belt had no such adenopathy. Thus, we hypothesize that previous fungal infection may predispose the lungs of certain patients to subsequent invasion by MAC, presumably by airway distortion and/or parenchymal damage.

Aged↗

Strategies in complex disease mapping.

Dissecting the genetics of common, complex disorders remains one of the great challenges in human genetics. The acceleration of human genome sequence determination, improvements in informatics, large-scale identification of single nucleotide polymorphisms and improvements in scoring technologies have now increased the feasibility of identifying polymorphisms that predispose to common disease.

Chromosome Mapping↗

An epidemiologic analysis of Mycobacterium avium complex disease in homosexual men infected with human immunodeficiency virus type 1.

Cofactors associated with the Mycobacterium avium complex (MAC) disease and its prognosis in incident cases of AIDS in homosexuals were studied. We compared 51 men in whom MAC disease developed as the initial AIDS-defining illness (termed AIDS illness hereafter); 157 men who had MAC disease subsequent to another AIDS illness; and 884 men who had only non-MAC AIDS illnesses. MAC disease was the initially diagnosed AIDS illness more often in Baltimore (6.9%) and Los Angeles (5.6%) than in Chicago (2.6%) and Pittsburgh (0) (P < .01). MAC disease also was a more common subsequent AIDS illness in Baltimore (14.3%) and Los Angeles (22.4%) than in Chicago (8.5%) and Pittsburgh (6.5%) (P < .0001). Prophylaxis for Pneumocystis carinii infection increased the occurrence of MAC disease as the initial AIDS illness (from 2.3% to 12.5%; P < .0001). A low white blood cell (WBC) count was slightly more predictive of MAC disease than was a low CD4+ cell count. At 0-6, 7-12, and 13-18 months before diagnosis, the WBC cell counts of 75.0%, 61.1%, and 50.0%, respectively, of those with MAC disease as the initial AIDS illness were < or = 3,400/microL. Men in whom cytomegalovirus disease developed were at higher risk for subsequent MAC disease (relative hazard = 2.65; P < .0001). MAC disease also increased the risk for subsequent cytomegalovirus disease (relative hazard = 3.96; P < .0001).

AIDS-Related Opportunistic Infections↗

[Clinical comparison of pulmonary tuberculosis with pulmonary M. avium complex disease].

At first, we reviewed radiographic findings of primary pulmonary tuberculosis, secondary pulmonary tuberculosis, pulmonary M. avium complex (MAC) disease without predisposing conditions, and pulmonary tuberculosis in AIDS patient. Infiltrates in lower field, mediastinal lymphadenopathy, and pleural effusion were the characteristics for primary pulmonary tuberculosis, while multiple nodular shadow with/without cavitation in S1,2,6 were the characteristics for secondary pulmonary tuberculosis. In pulmonary MAC disease without predisposing conditions, lesions progressed slowly from a cluster of a small nodules to cystic bronchiectasis with collapse of the segment or the lobe, and it took usually more than 10-years for the whole process interval. The characteristics of pulmonary tuberculosis in AIDS patient were nearly the same as those of primary pulmonary tuberculosis. Secondly, we compared clinical characteristics between pulmonary tuberculosis and pulmonary MAC disease. We reviewed the medical records of hospitalized patients who were diagnosed as pulmonary tuberculosis or pulmonary MAC disease. Systemic compromised host defense, such as diabetes mellitus or malignancy, played a more important predisposing factors in the development of pulmonary MAC disease. The average age of patients with MAC disease was found to be older than those with tuberculosis. By gender women were predominant in MAC disease, while men were predominant in tuberculosis.

AIDS-Related Opportunistic Infections↗

Disseminated Mycobacterium avium complex disease in the Swiss HIV Cohort Study: increasing incidence, unchanged prognosis.

OBJECTIVES: Disseminated disease due to Mycobacterium avium complex (MAC) bacteria is thought to occur less frequently in Europe than in the USA. This study investigated time trends in the occurrence of, and survival with, disseminated MAC disease in the Swiss HIV Cohort Study (SHCS). DESIGN, SETTING AND PARTICIPANTS: The SHCS participants who were free of disseminated MAC disease at registration were stratified by calendar period (1987-1989, 1990-1992, 1993-1995) in which the first recorded CD4 count was 0-49, 50-99, or 100-199 x 10(6)/l. Kaplan-Meier estimates of the probability of developing and surviving disseminated MAC disease were calculated for these nine independent groups. Multivariate analyses were performed using Cox proportional hazards regression. RESULTS: The analysis was based on 6052 participants enrolled between January 1987 and December 1995 and 202 incident episodes of disseminated MAC disease recorded during a mean follow-up time of 3.5 years. The cumulative probability of MAC disease at 2 years in individuals with CD4 counts of 0-49 x 10(6)/l in 1987-1989 was 9.8% [95% confidence interval (CI) 4.4-15.2%], increasing to 29.8% (95% CI, 20.8-38.8%) in 1993-1995. Amongst those with CD4 counts from 50-99 x 10(6)/l these probabilities were 11.9% (95% CI, 5.9-17.8%), and 21.6% (95% CI, 13.9-29.2%), respectively. After adjusting for CD4 count the relative hazard of developing disseminated MAC disease in 1993-1995, compared with 1987-1989, was 1.37 (95% CI, 0.92-2.04). Median survival following diagnosis was 7.9 months with no improvement over time. CONCLUSIONS: The incidence of disseminated MAC disease among SHCS participants has increased over time. More profound levels of immunosuppression amongst recent study entrants were found to explain this. When compared with US cohorts studied over the same calendar period the incidence of disseminated MAC disease in the SHCS appears to be lower. These findings are consistent with a secular effect of a more mature HIV epidemic in the US but direct comparison between the SHCS and a similar prospective cohort in the US should be undertaken to clarify this issue.

AIDS-Related Opportunistic Infections↗