A new mechanism for immunologic initiation of asthma

Kaplan, Allen P.

doi:10.1073/pnas.0409828102

Cited by 5 publications

(2 citation statements)

References 14 publications

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“…However, it still remains unclear whether FLCs interact with mast cells and, if so, which membrane receptor is involved. A possibility was also raised as to whether dimerization of FLCs is a necessary condition related to cross-linkage of membrane elements [44]. In respect to the latter argumentation, it is worth underscoring the significant elevation of the specific mast cell markers [35,37,45], as well as the increase in the level of FLC dimers in the CSF of MS patients [12], thus indicating a possible link between mast cell activation and enhanced FLC dimerization in MS.…”

Section: Function Of Flc Dimers In Human Diseasesmentioning

confidence: 99%

Immunoglobulin Free Light Chain Dimers in Human Diseases

Kaplan

Livneh

Sela

2011

The Scientific World JOURNAL

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Immunoglobulin free light chain (FLC) kappa (κ) and lambda (λ) isotypes exist mainly in monomeric and dimeric forms. Under pathological conditions, the level of FLCs as well as the structure of monomeric and dimeric FLCs and their dimerization properties might be significantly altered. The abnormally high fractions of dimeric FLCs were demonstrated in the serum of patients with multiple myeloma (MM) and primary systemic amyloidosis (AL), as well as in the serum of anephric patients. The presence of tetra- and trimolecular complexes formed due to dimer-dimer and dimer-monomer interactions was detected in the myeloma serum. Analysis of the amyloidogenic light chains demonstrated mutations within the dimer interface, thus raising the possibility that these mutations are responsible for amyloidogenicity. Increased κ monomer and dimer levels, as well as a high κ/λ monomer ratio, were typically found in the cerebrospinal fluid from patients with multiple sclerosis (MS). In many MS cases, the elevation of κ FLCs was accompanied by an abnormally high proportion of λ dimers. This review focuses on the disease-related changes of the structure and level of dimeric FLCs, and raises the questions regarding their formation, function, and role in the pathogenesis and diagnosis of human diseases.

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Section: Function Of Flc Dimers In Human Diseasesmentioning

confidence: 99%

Immunoglobulin Free Light Chain Dimers in Human Diseases

Kaplan

Livneh

Sela

2011

The Scientific World JOURNAL

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“…One of the most common allergen classification takes into consideration their molecular weight identifying low-molecular weight allergens (LMWA) < 5 kDa2 or < 10 kDa34 and high-molecular weight allergens (HMWA) > 5 kDa 2 or > 10 kDa 34. The majority of HMWA are proteins or glycopeptides, usually inducing allergic responses via immunoglobulin E (IgE)-mediated mechanism 56. Otherwise, LMWA are considered to be haptens (incomplete or remnant allergens) alone not able to induce IgE synthesis 7.…”

Section: Introductionmentioning

confidence: 99%

Bronchial Response to High and Low Molecular Weight Occupational Inhalant Allergens

Lipińska‐Ojrzanowska

Nowakowska‐Świrta

Wiszniewska

et al. 2020

Allergy Asthma Immunol Res

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PurposeOccupational asthma may be induced by high- or low-molecular weight allergens (HMWA or LMWA, respectively). The study was conducted to compare the pattern of bronchial response in 200 HMWA-induced asthmatics (n = 130) and LMWA-induced asthmatics (n = 70).MethodsThe study participants underwent a single-blind, placebo-controlled specific inhalation challenge (SIC) with workplace allergens, accompanied by evaluation of non-specific bronchial hyperresponsiveness (NSBHR) with methacholine before and after the SIC.ResultsA single early bronchial response more frequently occurred in HMWA-induced asthmatics than in LMWA-induced asthmatics (86.2% vs. 20%). An isolated late bronchial response or atypical patterns were more frequently observed in LMWA-induced asthmatics than in LMWA-induced asthmatics (45.7% vs. 3.8% or 34.3% vs. 10%, respectively). Baseline NSBHR before SIC was more often detected in LMWA-induced asthmatics than in HMWA-induced asthmatics (81.4% vs. 54.6%), and the median value of the provocation concentration of methacholine was relevantly lower in these patients before and after SIC. A significant 3-fold increase in NSBHR after SIC was observed more often in LMWA-induced asthmatics than in HMWA-induced asthmatics (82.8% vs. 66.1%). In addition, compared to LMWA-induced asthmatics, HMWA-induced asthmatics were older, were more frequently active smokers, showed lower level of NSBHR, and more frequently continued their work in harmful occupational exposure.ConclusionsThe results of this study suggest that HMWA-induced asthmatics may have milder clinical courses and that there is a possibility of job continuation despite asthma exacerbation requiring medical surveillance.

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