HLA class I and class II antigens associated with multiple myeloma in southern Africa.

While the exact aetiology of myeloma is unknown, genetic factors feature among the potential risk factors. The HLA phenotypes in African blacks with myeloma (the commonest haematopoietic malignancy in this group) have not been characterized. The purpose of this study was to determine the HLA class I and class II phenotypes of patients with multiple myeloma and to compare the findings to an ethnically matched control group of 100 individuals. Analysis of the HLA class I and class II phenotypes in 62 myeloma patients revealed: (i) a corresponding statistically significant association with HLA B18 [odds ratio (OR) 6.3; 95% confidence interval (CI) 1.013-39.727; P < 0.005]; (ii) no statistically significant association with HLA B13, Cw2, Cw6 or the DR and DQ antigens; and (iii) a statistically significant negative (protective) association with HLA Cw7 (OR 0.4; 95% CI 0.21-0.87; P < 0.005). This study suggests that although genetic factors may play a role in the multifactorial aetiology of multiple myeloma, with the exception of HLA B18, there is no specific association between HLA types and multiple myeloma in South African blacks.

Acute phase proteins in major depression.

Extensive evidence exists associating depression with changes in the immune system. The present study evaluates the levels of complement components C3 and C4, C-reactive proteins, and IL-6 in patients who met DSM-III-R diagnostic criteria for major depressive disorder, as well as controls. Whereas no significant differences between the mean levels of C3 could be detected between depressed patients and controls, the levels of C4, IL-6 (where detected), and C-reactive protein were significantly raised in the group with a depressive disorder. Our study suggests an interaction between psychological state and immune systems operative in host defenses.

IgG subclasses in previously healthy adult patients with acute community-acquired pneumonia.

OBJECTIVE: To measure IgG antibody subclasses in previously healthy adult patients with acute community-acquired pneumonia, and to assess any association between differences of subtype levels and severity of illness or prognosis. DESIGN: Prospective study. SETTING: The intensive care unit (ICU) and general medical wards of Hillbrow Hospital, Johannesburg, an urban general hospital. PATIENTS: Sixty-six previously healthy adult patients with acute community-acquired pneumonia, of whom 47 were considered less severely ill, while 19 were admitted to an ICU. OUTCOME MEASURES: Measurement of IgG subclass levels and determination of any association between differences in subtype levels and various poor prognostic factors in pneumonia, need for ICU admission, complications of illness, and APACHE II score of ICU cases or outcome of patients. RESULTS: A number of statistically significant differences (P < 0.05) were noted between the two groups of patients (critically ill v. others) representing well-known negative prognostic factors in pneumonia. A greater degree of tachycardia and tachypnoea and extremes of white cell count, a higher serum urea concentration and multilobar pulmonary consolidation characterised the patients in the ICU. In addition, the mortality rate in the ICU patients was significantly greater (P < 0.0001). Similar findings were noted when survivors and non-survivors were compared. Few abnormalities of IgG subclass levels were noted in the various patient groups, which did not allow adequate analysis of their clinical significance. CONCLUSION: This study demonstrated a small number of abnormalities in IgG subclass levels in previously healthy adult patients with acute community-acquired pneumonia.

The pro-oxidative riminophenazine B669 neutralizes the inhibitory effects of Mycobacterium tuberculosis on phagocyte antimicrobial activity.

The effects of clofazimine, a riminophenazine antimicrobial agent, and its analogue B669 on phagocyte functions have been investigated. Clofazimine, at concentrations attainable in vivo, and B669, in particular, increased the intracellular killing ability of phagocytes following appropriate cell stimulation. Similarly, nitro blue tetrazolium reduction, hydrogen peroxide production, lysosyme release and hexose monophosphate shunt activity were all increased by treating phagocytes with the riminophenazines. It has previously been shown that a 25 kDa glycolipoprotein derived from Mycobacterium tuberculosis inhibits phagocyte functions associated with phagocyte antimicrobial activity. The present study confirms these observations. A further aspect of the study examined the ability of riminophenazines to reverse the inhibition of phagocyte functions by the 25 kDa mycobacterial fraction. Whilst both riminophenazines were capable of partially but significantly reversing the inhibition due to the mycobacterial fraction, the restorative capacity of B669 was greater than that of clofazimine.

The inhibitory effects of Mycobacterium tuberculosis on MHC class II expression by monocytes activated with riminophenazines and phagocyte stimulants.

The expression of MHC class II antigens by peripheral blood monocytes from normal individuals was investigated. Class II expression as determined by a cell ELISA was effectively induced by various phagocyte stimulants. A further aspect of our study investigated the effects of clofazimine, a riminophenazine antimicrobial agent and its analogue, B669, on class II expression. Both agents at concentrations attainable in vivo increased the expression of MHC class II antigens. A 25-kD glycolipoprotein derived from Mycobacterium tuberculosis that inhibits phagocyte functions has previously been described. This component significantly reduced the expression of MHC class II antigens induced by the riminophenazines, clofazimine and B669, interferon-gamma (IFN-gamma) or opsonised yeast when added at the initiation of experiments. The riminophenazines could not restore the decrease in class II antigen expression previously inhibited by the 25-kD mycobacterial fraction. However, cultures prestimulated with the riminophenazines or phagocyte stimulants were unaffected by the 25-kD mycobacterial fraction. The results suggest the potential use of these agents as modulators of phagocyte function.

Suppression of cytokine production by supernatants from CD8+ lymphocytes activated by mycobacterial fractions: the role of interleukins 4 and 6.

Supernatants derived from CD8+ lymphocytes treated with mycobacterial components, or the partially purified carbohydrates from these supernatants, increased the production of IL-4 and IL-6 by mononuclear cells. The addition of anti-IL4 or anti-IL6 antibodies to LPS stimulated MN cells incubated with supernatants from CD8+ lymphocytes or carbohydrates resulted in the restoration of other cytokine production by these MN cells. Recombinant IL-4 and IL-6 on their own suppressed the production of IL-1 beta, TNF-alpha, IL-2 and IFN-gamma by mononuclear cells. Such suppression could be reversed with antibodies to IL-4 and IL-6. The addition of rIL-4 and rIL-6 did not increase the suppression of cytokine production induced by suppressor supernatants or carbohydrates. Interleukin 4 decreased the production of IL-6 by MN cells; whilst IL-6 suppressed IL-4 production in a dose dependent manner. Both effects could be reversed with the appropriate antisera. Our results suggest that mycobacteria could evade host immunity by inducing the production of IL-4 and IL-6 by host mononuclear cells. These cytokines, in turn, would suppress the production of other cytokines necessary for effective cellular immunity.