Reactivity to bacterial, fungal, and parasite antigens in patients with lymphedema and elephantiasis.

Abstract

Abstract. Both secondary infections and antifilarial immunity are thought to play roles in the development and progression of lymphedema. To investigate this issue, immune responses to a panel of bacterial, fungal, and parasite antigens were examined for women with lymphedema and elephantiasis (n ϭ 28) and for women with no clinical evidence of lymphatic dysfunction who were either microfilaremic (Mfϩ, n ϭ 23) or microfilaria-and filarial antigennegative (AgϪ, n ϭ 24). The prevalence and intensity of delayed-type hypersensitivity (DTH) responses was similar for most recall antigens; for individual antigens, lymphedema patients were significantly more likely to be reactive only to Proteus. Lymphedema patients with a history of three or more attacks of adenolymphangitis in the last 18 months showed increased DTH reactivity to Trichophyton. Proliferative responses to fungal and bacterial antigens were similar for all three groups; however, antigen-negative women, independent of disease status, mounted greater responses to filarial antigen. In contrast, lymphedema patients had higher levels of antifilarial specific IgG1, IgG2, and IgG3 and higher IgG responses to streptolysin O than either AgϪ or Mfϩ women. In persons with lymphatic filariasis, immune reactivity is influenced by disease status as well as infection status.

Characterization of Antibody Responses to Wolbachia Surface Protein in Humans with Lymphatic Filariasis

“…Recurrent bacterial infections that manifest as acute dermatolymphangioadenitis have been shown to contribute to the development of chronic lymphedema (11). In addition, patients with lymphedema have been shown to display heightened immune reactivity to bacterial antigens (especially streptolysin O) compared to infection-matched individuals without disease (2). This raises the question of the possible association between anti-Wolbachia immune responses and immune responses directed at other bacteria.…”

“…Additionally, host inflammatory responses stimulated by parasite antigens are thought to contribute to the development of disease (13); however, immune responses to adult worm extracts in these two groups are strongly associated with the patient's infection status. Although patients with lymphedema display the greatest levels of antifilarial immunity (2), similar types of responses are also seen in asymptomatic Ag Ϫ Mf Ϫ individuals (10). In addition, antifilarial immune responses among men with hydrocele are more closely associated with the patient's infection status than with the presence of disease (1).…”

“…As part of a previous study in our lab (2), immune responses of patients with lymphedema to various bacterial antigens were assayed. Among 25 Ag Ϫ Mf Ϫ women with lymphedema who were included in both this study and the previous study and for whom antibody data for WSP and other bacterial antigens were available, there were no differences in median IgG responses to Pseudomonas exotoxin (41 versus 17 arbitrary units; P ϭ 0.28), Staphylococcus enterotoxin B (202 versus 329 arbitrary units; P ϭ 0.19), Streptococcus group A antigen (78 versus 62 arbitrary units; P ϭ 0.55), or streptolysin O (131 versus 142 arbitrary units; P ϭ 0.83) between individuals who were anti-WSP ϩ and anti-WSP Ϫ , respectively.…”

Implications of Lymphatic Transport to Lymph Nodes in Immunity and Immunotherapy

“…Accordingly, altered immunity has been reported in primary lymphedema (110), highlighting the importance of lymphatic pathways in adaptive immune response in a variety of pathologies. Supporting this concept are observations of edematous limbs being more prone to infection (111, 112) and skin malignancies occurring at higher rates in lymphedematous limbs compared with nonlymphedematous sites in transplant patients (113).…”

Morbidity management in the Global Programme to Eliminate Lymphatic Filariasis: a review of the scientific literature

“…The relative infrequency with which bacteria are isolated from patients with ADLA [22,29,32], as well as from persons with cellulitis in areas not endemic for lymphatic filariasis [33,34], suggests a role for inflammatory mediators [33-35], perhaps even in the absence of bacteria.…”