Serum Th1/Th2 and macrophage lineage cytokines in leprosy; correlation with circulating CD4(+) CD25(high) FoxP3(+) T-regs cells.

Not only macrophages, T-helper (Th)1 and Th2, but also CD4(+) CD25(high) FoxP3(+) regulatory T cells (T-regs) are involved in immune response to Mycobacterium leprae. We aimed to evaluate serum interleukin (IL)-1ß and IL-12p70 (macrophage cytokines), interferon-γ (IFN-γ) (Th1 cytokine), IL-4 (Th2 cytokine) and circulating CD4(+) CD25(high) FoxP3(+) T-regs, in untreated leprosy patients. Forty three patients and 40 controls were assessed for the mentioned cytokines using ELISA. Patients were assessed for circulating T-regs using flow cytometry. Patients were subgrouped into tuberculoid (TT), pure neural leprosy (PNL), borderline cases, lepromatous (LL), type 1 reactional leprosy (RL1) and erythema nodosum leprosum (ENL). Serum IL-12p70, IFN-γ and IL-4 were significantly higher in patients versus controls (P < 0.05). Serum IL-4 was highest in LL and lowest in RL1 (P = 0.003). Serum IL-1ß levels was significantly higher in multibacillary versus paucibacillary patients (P = 0.006). Significantly higher T-regs levels was detected in TT, RL1 and PNL, while the lowest levels in ENL(P < 0.001), with significant differences versus controls (P < 0.05). FoxP3 expression% was significantly lower in PNL than other patients and controls (P < 0.05). T-regs/T-effs was lowest in ENL(P < 0.05). IFN-γ correlated positively with T-regs but negatively with IL-1ß (P = 0.041&0.046 respectively), which correlated positively with T-effs%( P = 0.05). IL-4 correlated positively with T-regs FoxP3 expression% (P = 0.009). We concluded that: Circulating T-regs were increased in TT, RL1 and PNL patients, known of relatively high cell-mediated immunity. This finding was supported by low FoxP3 expression (in PNL) and correlation between T-regs count and IFN-γ level. Overproduction of IL-4 in LL may infer liability to develop ENL, with disease progression and immune hyperactivation, marked by deficient T-regs and increased T-regs FoxP3 expression%. IL-1ß probably has a pro-inflammatory role in multibacillary patients as correlated with T-effs%.

Assessment of serum level of interleukin-1b and interleukin-12 in leprosy: impact of previous Bacillus Calmitte Guerin vaccination.

Macrophages play an important role in attempt to eliminate mycobacteria, via production of cytokines, including interleukin-1, and interleukin-12. Bacillus Calmitte Guerin (BCG) vaccination, known to induce interleukin-1ß in tuberculosis, was originally aimed at tuberculosis control, but it showed efficacy against leprosy. Our aim was to estimate serum levels of interleukin-1ß and interleukin-12, in leprosy, and to assess the impact of previous BCG vaccination on their levels. Serum interleukin-1ß and interleukin-12 p70 were estimated in 43 leprotic patients and 43 controls by enzyme-linked immunosorbent assay. Patients were grouped according to presence or absence of reactions, as well as bacillary load. Serum interleukin-1ß was significantly higher in patients as compared to controls (p = 0.047), and was significantly different in patients' groups (p = 0.036); with significantly higher level in multibacillary patients, both non reactional and with erythema nodosum leprosum, compared with paucibacillary/non reactional patients (p = 0.012 and 0.049 respectively). A statistically significant higher interleukin-1ß was found in BCG vaccinated paucibacillary patients as compared to unvaccinated patients (p = 0.031). Significantly elevated interleukin-12 was present in patients as compared to controls (p < 0.001), with no statistically significant difference comparing patients' groups. BCG vaccination showed stimulatory effect on monocytes only in the immunocompetent paucibacillary leprosy patients, as evidenced by higher Interleukin-1ß in this group. Interleukin-1ß was shown to have a pro-inflammatory role in multibacillary patients with or without erythema nodosum leprosum. Targeting interleukin-1ß may be promising to control episodic refractory erythema nodosum leprosum. Interleukin-12 may be a general marker of active Mycobacterium leprae infection.

Estimation of serum level of interleukin-17 and interleukin-4 in leprosy, towards more understanding of leprosy immunopathogenesis.

BACKGROUND: Combating Mycobacterium leprae is known to be via T-helper1 response. However, other T-helper effector cells; T-helper17 and T-helper2; play a role, particularly in the context of disease type. AIMS: We aimed to evaluate serum levels of interleukin (IL)-17 (T-helper17 cytokine) and IL-4 (T-helper2 cytokine) in untreated patients with different types of leprosy, compared to controls. METHODS: Using enzyme-linked immunosorbent assay, serum IL-17 and IL-4 levels were estimated in 43 leprotic patients and 43 controls. Patients were divided into six groups; tuberculoid, borderline cases, lepromatous, erythema nodosum leprosum (ENL), type 1 reactional leprosy, and pure neural leprosy. Patients were also categorized according to bacillary load and the presence or absence of reactions. RESULTS: Serum IL-17 was significantly lower in cases (4-61.5 pg/mL; median 19), compared to controls (26-55 pg/mL; median 36) (P < 0.001), and was significantly lower in each type of leprosy compared to controls, with the lowest level in lepromatous leprosy (4-61.5 pg/mL; median 12.5). Significantly elevated serum IL-4 was found in patients (1.31-122.4 pg/mL; median 2.31) compared to controls (1.45-5.72 pg/mL; median 2.02) (P = 0.008), with the highest level among lepromatous leprosy patients (2-87.2 pg/mL; median 28.9), and the lowest in type 1 reactional leprosy (1.4-2.5 pg/mL; median 1.87) (P = 0.006). CONCLUSION: Defective secretion of IL-17 is related to disease acquisition as well as progression toward lepromatous pole in leprosy patients. The overproduction of IL-4 in patients with lepromatous leprosy may infer their liability to develop ENL. Nevertheless, the small number of the studied population is a limitation.

Multiple isolated cutaneous plexiform schwannomas.

Plexiform schwannoma is a rare neurogenic tumor, arising from skin and subcutaneous tissue. The presence of multiple schwannomas suggests a possible association with neurofibromatosis type 2 (NF2). A 50-year old male patient presented with multiple papulo-nodular cutaneous lesions on both arms and forearms. Histopathological examination revealed a dermal multinodular pattern of well-circumscribed masses of closely packed cells, with peripheral myxoid tissue, well-encapsulated in a thin collagenous capsule. S-100 immunohistochemical staining was diffusely and strongly positive. Neuron-specific enolase was positive, confirming a neural tissue tumor. An audiogram and Magnetic Resonance Imaging (MRI) of cerebro-pontine angle showed no detected abnormality, excluding acoustic neuroma. Thus, we present a case of multiple bilateral isolated cutaneous plexiform schwannomas, not associated with NF2. Multiple plexiform schwannomas is a very rare entity, distinct from neurofibromatosis (NF), and being confined to the dermis is even more rarely reported.

Circulating CD4+ CD25 high FoxP3+ T cells vary in different clinical forms of leprosy.

BACKGROUND: CD4(+) CD25(high) FoxP3(+) regulatory T cells (T-regs) were reported to increase in chronic infections. We aimed at studying their frequency in leprosy to investigate their role during Mycobacterium leprae infection. METHODS: Using flow cytometry, the frequency and FoxP3 expression of circulating T-regs was assessed in 38 leprosy patients and 38 healthy controls. Patients were divided into; group I tuberculoid (TT), group II borderline cases [borderline tuberculoid (BT), borderline (BB), and borderline lepromatous (BL)], group III lepromatous (LL), and group IV erythema nodosum leprosum (ENL). RESULTS: Mean T-regs% and FoxP3 expression were significantly elevated in patients (particularly TT) compared to controls (3.8 ± 2.5% vs. 2.5 ± 0.8% and 78.8 ± 56.2% vs. 55.8 ± 15.7%, respectively) (P < 0.05). Comparing the four disease groups, T-regs% was significantly different (median 5.3% in group I, 3.4% in group II, 2.8% in group III, and 1.2% in group IV; P = 0.005). FoxP3% on T-regs was not significantly different between them [median 71.5% in TT, 62.3% in borderline categories, 67.75% in LL, and 85.75% in ENL; P = 0.149). Notably FoxP3 expression was significantly higher in ENL than controls (P = 0.011). CONCLUSION: The frequency and suppressive marker of circulating T-regs are elevated in TT patients. Patients with LL and ENL express significantly lower frequency of T-regs and higher FoxP3 expression (in ENL), consistent with disease progression and immune hyper-activation in these disease categories. Thus, rather than being detrimental to immunity, intact T-regs activity may be beneficial to leprosy patients.