Review

Authors: Chen S Tan, Igor J Koralnik

Progressive multifocal leukoencephalopathy (PML) is a rare but often fatal brain disease caused by reactivation of the polyomavirus JC. Knowledge of the characteristics of PML has substantially expanded since the introduction of combination antiretroviral therapy during the HIV epidemic and the development of immune reconstitution inflammatory syndrome (IRIS) in patients with PML. Recently, the monoclonal antibodies natalizumab, efalizumab, and rituximab--used for the treatment of multiple sclerosis, psoriasis, haematological malignancies, Crohn's disease, and rheumatic diseases--have been associated with PML. Additionally, the JC virus can also lead to novel neurological disorders such as JC virus granule cell neuronopathy and JC virus encephalopathy, and might also cause meningitis. The increasingly diverse populations at risk and the recent discovery of the presence of the JC virus in the grey matter invite us to reappraise the pathogenesis of this virus in the CNS.

Topics: Humans; JC Virus; Leukoencephalopathy, Progressive Multifocal; Polyomavirus Infections; Tumor Virus Infections

PubMed: 20298966
DOI: 10.1016/S1474-4422(10)70040-5

Review

Authors: Joseph D Spahn, Christopher E Brightling, Paul M O'Byrne...

BACKGROUND

Airway hyperresponsiveness (AHR) is a key feature of asthma. Biologic therapies used to treat asthma target specific components of the inflammatory pathway, and their effects on AHR can provide valuable information about the underlying disease pathophysiology. This review summarizes the available evidence regarding the effects of biologics on allergen-specific and non-allergen-specific airway responses in patients with asthma.

METHODS

We conducted a systematic review in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, including risk-of-bias assessment. PubMed and Ovid were searched for studies published between January 1997 and December 2021. Eligible studies were randomized, placebo-controlled trials that assessed the effects of biologics on AHR, early allergic response (EAR) and/or late allergic response (LAR) in patients with asthma.

RESULTS

Thirty studies were identified for inclusion. Bronchoprovocation testing was allergen-specific in 18 studies and non-allergen-specific in 12 studies. Omalizumab reduced AHR to methacholine, acetylcholine or adenosine monophosphate (3/9 studies), and reduced EAR (4/5 studies) and LAR (2/3 studies). Mepolizumab had no effect on AHR (3/3 studies), EAR or LAR (1/1 study). Tezepelumab reduced AHR to methacholine or mannitol (3/3 studies), and reduced EAR and LAR (1/1 study). Pitrakinra reduced LAR, with no effect on AHR (1/1 study). Etanercept reduced AHR to methacholine (1/2 studies). No effects were observed for lebrikizumab, tocilizumab, efalizumab, IMA-638 and anti-OX40 ligand on AHR, EAR or LAR; benralizumab on LAR; tralokinumab on AHR; and Ro-24-7472 on AHR or LAR (all 1/1 study each). No dupilumab or reslizumab studies were identified.

CONCLUSION

Omalizumab and tezepelumab reduced EAR and LAR to allergens. Tezepelumab consistently reduced AHR to methacholine or mannitol. These findings provide insights into AHR mechanisms and the precise effects of asthma biologics. Furthermore, findings suggest that tezepelumab broadly targets allergen-specific and non-allergic forms of AHR, and the underlying cells and mediators involved in asthma.

PubMed: 37496824
DOI: 10.2147/JAA.S410592

Review

Authors: Kelly M Luba, Daniel L Stulberg

Chronic plaque psoriasis, the most common form of psoriasis, is a papulosquamous disease defined by erythematous plaques with a silvery scale. The diagnosis usually is clinical, but occasionally a biopsy is necessary. Psoriasis affects 0.6 to 4.8 percent of the U.S. population, and about 30 percent of affected patients have a first-degree relative with the disease. Psoriasis is a T-cell-mediated autoimmune disease, but certain medications and infections are well-known risk factors. Management of psoriasis includes education about chronicity, realistic expectations, and use of medication. Steroids and vitamin D derivatives (e.g., calcipotriene) are the mainstays of topical therapy. Topical steroids and calcipotriene together may work better than either agent alone. Patients with psoriasis involving more than 20 percent of their skin or those not responding to topical therapy are candidates for light therapy; traditional systemic therapy; or systemic treatment with immunomodulatory drugs such as alefacept, efalizumab, and etanercept.

Topics: Algorithms; Calcitriol; Chronic Disease; Comorbidity; Dermatologic Agents; Humans; Psoriasis; Risk Factors; Ultraviolet Therapy

PubMed: 16506705
DOI: No ID Found

Authors: Steven Feldman

Topics: Adrenal Cortex Hormones; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Drug-Related Side Effects and Adverse Reactions; Female; Health Knowledge, Attitudes, Practice; Humans; Male; Physician-Patient Relations; Risk Assessment; Skin Diseases

PubMed: 19319706
DOI: 10.1080/09546630902857966

Review

Authors: Mohamed Adel Bakr, Ayman Maher Nagib, Ahmed Farouk Donia...

Induction therapy after kidney transplantation is intensive immunosuppression in the initial days after transplant when the immune system of the recipient has the first contact with donor antigens. Initial intensive immunosuppression may be required to prevent acute rejection and graft loss, and subsequent immunosuppression may be decreased to minimize adverse events associated with immunosuppressive drugs. Induction agents include lymphocyte-depleting antibodies such as rabbit antithymocyte globulin, alemtuzumab, muromonab-CD3, rituximab, and bortezomib; lymphocyte-nondepleting antibodies such as interleukin 2 receptor antibodies; and other discontinued or investigational agents such as efalizumab and alefacept. Induction therapy may be adjusted for special situations such as living-donor kidney transplant, pediatric transplant, hepatitis C virus-seropositive recipients, recipients who require desensitization, patients who are at risk for developing delayed graft function, and old donors. The optimal immunosuppressive regimen may vary, and clinical practice guidelines are available.

Topics: Acute Disease; Drug Administration Schedule; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Kidney Transplantation; Patient Selection; Risk Factors; Time Factors; Treatment Outcome

PubMed: 24635795
DOI: 10.6002/ect.25liver.l58

Review

Authors: Ivan Jelcic, Ilijas Jelcic, Wolfgang Faigle...

The high prevalence of asymptomatic JC polyomavirus (JCV) infection in the general population indicates coexistence with the human host and efficient immune control in healthy individuals. For unknown reasons, kidney-resident archetypic JCV strains can turn into neurotropic JCV strains which in hereditary or acquired states of immunodeficiency cause opportunistic infection and cytolytic destruction of glial cells or granule cell neurons resulting in progressive multifocal demyelination in the central nervous system (CNS) or cerebellar atrophy, respectively. Immunomodulatory or immunosuppressive therapies with specific monoclonal antibodies including natalizumab, efalizumab, and rituximab have increased the risk of progressive multifocal leukoencephalopathy (PML) among treated patients, highlighting that symptomatic JCV infection of the CNS is associated with disturbances of adaptive immunity affecting B cells, antibodies, and CD4(+) and/or CD8(+) T cells. To date, no specific therapy to overcome PML is available and the only way to eliminate the virus from the CNS is to reconstitute global immune function. However, since the identification of JCV as the causative agent of PML 40 years ago, it is still not fully understood which components of the immune system prevent the development of PML and which immune mechanisms are involved in eliminating the virus from the CNS. This review gives an update about adaptive JCV-specific immune responses.

Topics: Humans; JC Virus; Leukoencephalopathy, Progressive Multifocal

PubMed: 25740538
DOI: 10.1007/s13365-014-0294-y

Authors: Janice M Reichert

Therapeutic monoclonal antibodies (mAbs) are currently being approved for marketing in Europe and the United States, as well as other countries, on a regular basis. As more mAbs become available to physicians and patients, keeping track of the number, types, production cell lines, antigenic targets, and dates and locations of approvals has become challenging. Data are presented here for 34 mAbs that were approved in either Europe or the United States (US) as of March 2012, and nimotuzumab, which is marketed outside Europe and the US. Of the 34 mAbs, 28 (abciximab, rituximab, basiliximab, palivizumab, infliximab, trastuzumab, alemtuzumab, adalimumab, tositumomab-I131, cetuximab, ibrituximab tiuxetan, omalizumab, bevacizumab, natalizumab, ranibizumab, panitumumab, eculizumab, certolizumab pegol, golimumab, canakinumab, catumaxomab, ustekinumab, tocilizumab, ofatumumab, denosumab, belimumab, ipilimumab, brentuximab) are currently marketed in Europe or the US. Data for six therapeutic mAbs (muromonab-CD3, nebacumab, edrecolomab, daclizumab, gemtuzumab ozogamicin, efalizumab) that were approved but have been withdrawn or discontinued from marketing in Europe or the US are also included.

Topics: Animals; Antibodies, Monoclonal; Drug Approval; Europe; Humans; Immunotherapy; Marketing; Product Recalls and Withdrawals; United States

PubMed: 22531442
DOI: 10.4161/mabs.19931

Review

Authors: Benjamin F Chong, Henry K Wong

The pathogenesis of various inflammatory cutaneous diseases such as psoriasis, atopic dermatitis and mycosis fungoides relies greatly on the abnormal function of T cells. Fundamental knowledge of the role of T cells in the cutaneous immune response has led to the development and production of biologic molecules designed to block T cell function at various steps, specifically activation (i.e. alefacept, efalizumab), trafficking into inflamed skin (i.e. efalizumab) and effector function under cytokine control (i.e. etanercept, infliximab, adalimumab, and anti-IL-12 antibody). We review the immune abnormalities and the role of T cells in psoriasis, and the recent biologic therapies, which share the common mission to hinder T cell activity in inflammatory diseases. An advantage from the preciseness of these biologic therapies is the potential limit of non-specific and potentially devastating organ toxicity, which commonly plagues other systemic therapies.

Topics: Alefacept; Antibodies, Monoclonal; Cell Movement; Dermatologic Agents; Etanercept; Humans; Immunoglobulin G; Immunotherapy; Lymphocyte Activation; Psoriasis; Receptors, Tumor Necrosis Factor; Recombinant Fusion Proteins; T-Lymphocytes

PubMed: 17317321
DOI: 10.1016/j.clim.2007.01.006