The frequencies of antibody development so far reported in patients treated with different interferons (IFNs) are not readily comparable because of differences in treatment regimens and assay methods. Thus the frequency of neutralizing antibody development was analyzed in a large sample of sera derived from a relatively homogeneous group of patients treated with different IFN-alpha preparations. The frequency of developing neutralizing antibody to IFN varied according to the IFN given. Particularly, the seroconversion frequency was significantly higher in patients treated with recombinant IFN-alpha 2a (20.2%) than in patients treated with either recombinant IFN-alpha 2b (6.9%) or IFN-alpha N1 (1.2%), a lymphoblastoid IFN-alpha. Furthermore, sera obtained from patients treated with either recombinant IFN neutralized both types of recombinant IFNs but failed to neutralize IFN-alpha N1.

/pdf/neutralizing-antibodies-to-interferon-alpha-relative-uduluhxfpy.pdf

Neutralizing antibodies to interferon-alpha: relative frequency in patients treated with different interferon preparations.

A retrospective chart review was conducted to determine the effect of alpha-Interferon (alpha-IFN) on disease progresssion, symptom palliation, and survival in HIV-associated Progressive Multifocal...

/pdf/survival-prolongation-in-hiv-associated-progressive-1x27ttt1lw.pdf

Survival prolongation in HIV-associated progressive multifocal leukoencephalopathy treated with alpha-interferon: an observational study.

It is known that IFN therapy can induce the development of anti-IFN antibodies. In order to evaluate the biological and clinical significance of both neutralizing (NA) and non-neutralizing (binding) antibodies, 123 patients with chronic hepatitis C treated with recombinant IFN-alpha were examined. Among them, 15 were positive for NA and 24 for binding antibodies. The kinetics of NA appearance show that, in general, they develop early during the first 3 months of treatment. Moreover, NA seem to be clinically relevant, since they may be responsible for non-responsiveness to treatment in 53% of patients who develop them. The evaluation of the clinical significance of binding antibodies is more difficult. They appear significantly earlier in non-responders than in responders, but no differences were observed in the overall percentage of seroconversion between responders and non-responders. Thus, it is not possible at the moment to establish their possible role in inducing non-responsiveness.

Biological and clinical significance of neutralizing and binding antibodies to interferon‐alpha (IFN–α) during therapy for chronic hepatitis C

BACKGROUND Prolonged therapy with interferon (IFN) may lead to the formation of IFN antibodies. METHODS Patients with renal cell carcinoma (n = 270) with advanced localized disease were randomized after complete tumor resection to receive treatment with adjuvant recombinant IFN-alpha-2a (rIFN-alpha 2a) (9 x 10(6) IU subcutaneously, three times per week for a maximum of 12 months) versus no treatment. Patients (IFN-treated group, 106 patients; control group, 97 patients) were monitored for the presence of rIFN-alpha 2a antibodies. RESULTS Of 86 IFN-treated patients observed for more than 2 months, 40 (47%) had IFN-alpha 2a-binding and 25 (29%) had IFN-alpha 2a-neutralizing antibodies developed within a median of 3 and 6 months, respectively. A distinct peak in binding antibody titers occurred at 6-9 months. Therapy-induced neutralizing antibodies were equally reactive with two other recombinant IFN-alpha-2 subtypes but poorly recognized natural IFN-alpha (IFN-alpha), recombinant IFN-alpha-1/alpha-8, and recombinant IFN-omega-1. The duration of remission and rate of relapse were independent of the antibody status, although neutralizing and most non-neutralizing antibodies correlated with a reduction in the IFN-induced increase in beta-2-microglobulin levels. CONCLUSIONS Patients treated with IFN-alpha 2a should be monitored for the presence and clinical relevance of IFN-alpha antibodies to determine those who could respond to alternative treatment.

Interferon‐alpha antibodies in patients with renal cell carcinoma treated with recombinant interferon‐alpha‐2A in an adjuvant multicenter trial

Development of neutralizing and binding antibodies to interferon (IFN) in patients undergoing IFN therapy.

Patients receiving large amounts of interferon (IFN), particularly cloned IFN-alpha, have been reported to develop antibodies to IFN-alpha. We used a neutralization technique bioassay to monitor 175 patients undergoing recombinant (r) IFN-alpha 2b therapy in an attempt to correlate antibody production to disease progression. Only 1 patient being treated for chronic myelogenic leukemia produced antibodies. Our findings indicate that rIFN-alpha 2b has minimal antigenicity, even when administered for prolonged periods of time.

Low incidence of neutralizing antibody formation to interferon-alpha 2b in human recipients.

A23187 in combination with phorbol myristate acetate (PMA) strongly induces production of interferon-gamma (IFN-gamma) by human peripheral blood mononuclear cells (PBMC) and even by murine PBMC, which respond poorly to A23187 alone. Macrophage depletion of PBMC strongly reduces IFN-gamma production induced by several mitogens, but does not affect IFN-gamma production induced by A23187 and PMA. In addition the same stimuli are able in combination to induce strong amounts of IFN-gamma, even in the Jurkat T cell line. The protein kinase C inhibitor 1-(5-isoquinolinylsulfonyl)-2-methyl-piperazine (H-7) and the calmodulin antagonist N-(6-aminoehexyl)-5-chloro-1-naphthalenesulfonamide (W-7) were examined for their ability to inhibit IFN-gamma production induced by PMA and A23187. At concentrations near the Ki for protein kinase C, H-7 failed to inhibit PMA- and A23187-induced IFN-gamma production. In contrast, W-7 at low concentrations inhibited IFN-gamma production induced by the same stimuli. In addition OAG, which is known to directly activate protein kinase C, failed to act synergistically with A23187 in the induction of IFN-gamma. On the basis of these results we propose that A23187 and PMA may mimic the early steps of lymphocyte activation, without the requirement of macrophage, bypassing antigen-, or lectin-induced signal. Our results suggest that Ca2+-calmodulin-dependent reactions other than protein kinase C activation may be essential for IFN-gamma production, at least at level of the producing cells.

Early steps in interferon-gamma production: possible involvement of Ca2+-calmodulin-dependent enzymes.

The surgical approach to chronic pilonidal disease has been significantly changed by minimally invasive and targeted procedures, with the aim to minimize costs and favoring less dressings, faster recovery, and prompt return to work or to school activity. Less invasive procedures are gaining wide acceptance as first approach. We present a single-center experience with the Gips technique, also called Israeli technique or trephine technique, and a brief review of the literature, focusing on minimally invasive procedures. KEY WORDS: Pilonidal Disease, Punch, Minimally Invasive Surgery, Trephines.

Pilonidal sinus disease. A single center retrospective series analysis.

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Low incidence of neutralizing antibody formation to interferon-alpha 2b in human recipients.

Early steps in interferon-gamma production: possible involvement of Ca2+-calmodulin-dependent enzymes.

Pilonidal sinus disease. A single center retrospective series analysis.