The third complementary-determining regions of the heavy-chain (CDR3H) variable regions (VH) of some cattle antibodies are highly extended, consisting of 48 or more residues. These `ultralong' CDR3Hs form β-ribbon stalks that protrude from the surface of the antibody with a disulfide cross-linked knob region at their apex that dominates antigen interactions over the other CDR loops. The structure of the Fab fragment of a naturally paired bovine ultralong antibody (D08), identified by single B-cell sequencing, has been determined to 1.6 Å resolution. By swapping the D08 native light chain with that of an unrelated antigen-unknown ultralong antibody, it is shown that interactions between the CDR3s of the variable domains potentially affect the fine positioning of the ultralong CDR3H; however, comparison with other crystallo­graphic structures shows that crystalline packing is also a major contributor. It is concluded that, on balance, the exact positioning of ultralong CDR3H loops is most likely to be due to the constraints of crystal packing.

During HIV infection, the virus mutates too rapidly for the immune system to combat, but some people produce antibodies that can recognize the virus even two years after infection. With an eye towards developing a vaccine, in four related papers from multiple groups publishing September 8 in Cell and Immunity, researchers describe a multi-step method for "training" the immune system to produce these antibodies in genetically engineered mice.

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Our immune systems generate antibodies that neutralize and help eliminate foreign pathogens. These antibodies or proteins are generated by specific immune

Monoclonal antibodies (mAbs) have revolutionized targeted cancer therapies with unmatched specificity and potency. Since the first mAb approval in 1986, ad

Our immune systems generate antibodies that neutralize and help eliminate foreign pathogens. These antibodies or proteins are generated by specific immune

Our immune systems generate antibodies that neutralize and help eliminate foreign pathogens. These antibodies or proteins are generated by specific immune

Reliable, specific polyclonal and monoclonal antibodies are important tools in research and medicine. However, the discovery of antibodies against their targets in their native forms is difficult. Here, we present a novel method for discovery of antibodies against membrane proteins in their native configuration in mammalian cells. The method involves the co-expression of an antibody library in a population of mammalian cells that express the target polypeptide within a natural membrane environment on the cell surface. Cells that secrete a single-chain fragment variable (scFv) that binds to the target membrane protein thereby become self-labeled, enabling enrichment and isolation by magnetic sorting and FRET-based flow sorting. Library sizes of up to 109 variants can be screened, thus allowing campaigns of naïve scFv libraries to be selected against membrane protein antigens in a Chinese hamster ovary cell system. We validate this method by screening a synthetic naïve human scFv library against Chinese hamster ovary cells expressing the oncogenic target epithelial cell adhesion molecule and identify a panel of three novel binders to this membrane protein, one with a dissociation constant (KD) as low as 0.8 nm. We further demonstrate that the identified antibodies have utility for killing epithelial cell adhesion molecule–positive cells when used as a targeting domain on chimeric antigen receptor T cells. Thus, we provide a new tool for identifying novel antibodies that act against membrane proteins, which could catalyze the discovery of new candidates for antibody-based therapies.

Xiao-Ting Wen
Dec 17, 2020; 0:RA120.002119v1-mcp.RA120.002119
Research

Some cases of chylomicronemia are caused by autoantibodies against glycosylphosphatidylinositol-anchored HDL binding protein 1 (GPIHBP1), an endothelial cell protein that shuttles LPL to the capillary lumen. GPIHBP1 autoantibodies prevent binding and transport of LPL by GPIHBP1, thereby disrupting the lipolytic processing of triglyceride-rich lipoproteins. Here, we review the "GPIHBP1 autoantibody syndrome" and summarize clinical and laboratory findings in 22 patients. All patients had GPIHBP1 autoantibodies and chylomicronemia, but we did not find a correlation between triglyceride levels and autoantibody levels. Many of the patients had a history of pancreatitis, and most had clinical and/or serological evidence of autoimmune disease. IgA autoantibodies were present in all patients, and IgG4 autoantibodies were present in 19 of 22 patients. Patients with GPIHBP1 autoantibodies had low plasma LPL levels, consistent with impaired delivery of LPL into capillaries. Plasma levels of GPIHBP1, measured with a monoclonal antibody–based ELISA, were very low in 17 patients, reflecting the inability of the ELISA to detect GPIHBP1 in the presence of autoantibodies (immunoassay interference). However, GPIHBP1 levels were very high in five patients, indicating little capacity of their autoantibodies to interfere with the ELISA. Recently, several GPIHBP1 autoantibody syndrome patients were treated successfully with rituximab, resulting in the disappearance of GPIHBP1 autoantibodies and normalization of both plasma triglyceride and LPL levels. The GPIHBP1 autoantibody syndrome should be considered in any patient with newly acquired and unexplained chylomicronemia.

Ankylosing Spondylitis (AS) is a common, inflammatory rheumatic disease, which primarily affects the axial skeleton and is associated with sacroiliitis, uveitis and enthesitis. Unlike other autoimmune rheumatic diseases, such as rheumatoid arthritis or systemic lupus erythematosus, autoantibodies have not yet been reported to be a feature of AS. We therefore wished to determine if plasma from patients with AS contained autoantibodies and if so, characterize and quantify this response in comparison to patients with Rheumatoid Arthritis (RA) and healthy controls. Two high-density nucleic acid programmable protein arrays expressing a total of 3498 proteins were screened with plasma from 25 patients with AS, 17 with RA and 25 healthy controls. Autoantigens identified were subjected to Ingenuity Pathway Analysis in order to determine patterns of signalling cascades or tissue origin. 44% of patients with Ankylosing Spondylitis demonstrated a broad autoantibody response, as compared to 33% of patients with RA and only 8% of healthy controls. Individuals with AS demonstrated autoantibody responses to shared autoantigens, and 60% of autoantigens identified in the AS cohort were restricted to that group. The AS patients autoantibody responses were targeted towards connective, skeletal and muscular tissue, unlike those of RA patients or healthy controls. Thus, patients with AS show evidence of systemic humoral autoimmunity and multispecific autoantibody production. Nucleic Acid Programmable Protein Arrays constitute a powerful tool to study autoimmune diseases.

Antibodies play essential roles in both diagnostics and therapeutics. Epitope mapping is essential to understand how an antibody works and to protect intellectual property. Given the millions of antibodies for which epitope information is lacking, there is a need for high-throughput epitope mapping. To address this, we developed a strategy, Antibody binding epitope Mapping (AbMap), by combining a phage displayed peptide library with next generation sequencing. Using AbMap, profiles of the peptides bound by 202 antibodies were determined in a single test, and linear epitopes were identified for >50% of the antibodies. Using spike protein (S1 and S2)-enriched antibodies from the convalescent serum of one COVID-19 patient as the input, both linear and conformational epitopes of spike protein specific antibodies were identified. We defined peptide-binding profile of an antibody as the Binding Capacity (BiC). Conceptually, the BiC could serve as a systematic and functional descriptor of any antibody. Requiring at least one order of magnitude less time and money to map linear epitopes than traditional technologies, AbMap allows for high-throughput epitope mapping and creates many possibilities.

To identify novel autoantibodies of Takayasu arteritis (TAK) using HuProt array-based approach. A two-phase approach was adopted. In Phase I, serum samples collected from 40 TAK patients, 15 autoimmune disease patients, and 20 healthy subjects were screened to identify TAK-specific autoantibodies using human protein (HuProt) arrays. In Phase II, the identified candidate autoantibodies were validated with TAK-focused arrays using an additional cohort comprised of 109 TAK patients, 110 autoimmune disease patients, and 96 healthy subjects. Subsequently, the TAK-specific autoantibodies validated in Phase II were further confirmed using Western blot analysis. We identified and validated eight autoantibodies as potential TAK-specific diagnostic biomarkers, including anti-SPATA7, -QDPR, -SLC25A2, -PRH2, -DIXDC1, -IL17RB, -ZFAND4, and -NOLC1 antibodies, with AUC of 0.803, 0.801, 0.780, 0.696, 0.695, 0.678, 0.635 and 0.613, respectively. SPATA7 could distinguish TAK from healthy and disease controls with 73.4% sensitivity at 85.4% specificity, while QDPR showed 71.6% sensitivity at 86.4% specificity. SLC25A22 showed the highest sensitivity of 80.7%, but at lower specificity of 67.0%. In addition, PRH2, IL17RB and NOLC1 showed good specificities of 88.3%, 85.9% and 86.9%, respectively, but at lower sensitivities (<50%). Finally, DIXDC1 and ZFAND4 showed moderate performance as compared with the other autoantibodies. Using a decision tree model, we could reach a specificity of 94.2% with AUC of 0.843, a significantly improved performance as compared to that by each individual biomarker. The performance of three autoantibodies, namely anti-SPATA7, -QDPR and -PRH2, were successfully confirmed with Western blot analysis. Using this two-phase strategy, we identified and validated eight novel autoantibodies as TAK–specific biomarker candidates, three of which could be readily adopted in a clinical setting.

Bispecific antibodies (bsAbs) are engineered to target 2 different epitopes simultaneously. About 75% of the 16 clinically approved bsAbs have entered the clinic internationally since 2022. Hence, research on biomedical imaging of various radiolabeled bsAb scaffolds may serve to improve patient selection for bsAb therapy. Here, we provide a comprehensive overview of recent advances in radiolabeled bsAbs for imaging via PET or SPECT. We compare direct targeting and pretargeting approaches in preclinical and clinical studies in oncologic research. Furthermore, we show preclinical applications of imaging bsAbs in neurodegenerative diseases. Finally, we offer perspectives on the future directions of imaging bsAbs based on their challenges and opportunities.

Donna M. Wilcock
May 1, 2003; 23:3745-3751
Development Plasticity Repair

Blood tests have shown that about 7 per cent of workers on dairy farms that had H5N1 outbreaks had antibodies against the disease

Title: Longer, Worse COVID Leaves Stronger Antibodies: Study
Category: Health News
Created: 8/23/2021 12:00:00 AM
Last Editorial Review: 8/23/2021 12:00:00 AM

Blood tests have shown that about 7 per cent of workers on dairy farms that had H5N1 outbreaks had antibodies against the disease

Blood tests have shown that about 7 per cent of workers on dairy farms that had H5N1 outbreaks had antibodies against the disease

Monoclonal antibodies are the antibodies produced in the laboratory which can increase, copy, or restore the immune system's response to certain antigens.

Transplanted hearts functioned longer in mice when the recipients who received the organs were administered with the novel antibody treatment before the surgery.

Monoclonal antibodies (mAbs) are special proteins used to help prevent, detect, and treat a wide range of diseases, both infectious and non-infectious.

According to research led by the Barcelona Institute for Global Health (ISGlobal) in partnership with seven African centers, maternal antibodies transferred

An extended analysis of structural ensembles obtained from small-angle X-ray scattering data reveals subclass-specific conformational preferences of IgG antibodies, which are largely determined by the hinge-region structure.

Most people infected with the novel coronavirus develop antibodies in response.

But scientists don't know whether people who have been exposed to the coronavirus will be immune for life, as is usually the case for the measles, or if the disease will return again and again, like the common cold.

"This to me is one of the big unanswered questions that we have," says Jeffrey Shaman, a professor of environmental health sciences at Columbia University, "because it really says, 'What is the full exit strategy to this and how long are we going to be contending with it?' "

He's one of many scientists on a quest for answers. And the pieces are starting to fall into place.

Antibodies, which are proteins found in the blood as part of the body's immune response to infection, are a sign that people could be developing immunity. But they are by no means a guarantee they will be protected for life – or even for a year.

Shaman has been studying four other coronaviruses that cause the common cold. "They're very common and so people seem to get them quite often," Shaman says. Ninety percent of people develop antibodies to those viruses, at least in passing, but "our evidence is those antibodies are not conferring protection."

That may simply because colds are relatively mild, so the immune system doesn't mount a full-blown response, suggests Dr. Stanley Perlman, a pediatrician who studies immunology and microbiology at the University of Iowa. "That's why people get colds over and over again," he says. "It doesn't really tickle the immune response that much."

He's studied one of the most severe coronaviruses, the one that causes SARS, and he's found that the degree of immunity depended on the severity of the disease. Sicker people remained immune for much longer, in some cases many years.

For most people exposed to the novel coronavirus, "I think in the short term you're going to get some protection," Perlman says. "It's really the time of the protection that matters."

Perlman notes that for some people the symptoms of COVID-19 are no worse than a cold, while for others they are severe. "That's why it's tricky," he says, to predict the breadth of an immune response.

And it's risky to assume that experiences with other coronaviruses are directly applicable to the new one.

"Unforutunately, we cannot really generalize what kind of immunity is needed to get protection against a virus unless we really learn more about the virus," says Akiko Iwasaki, a Howard Hughes Medical Institute investigator at the Yale University School of Medicine.

An immunobiologist, she is part of a rapidly expanding effort to figure this out. She and her colleagues are already studying the immune response in more than 100 patients in the medical school hospital. She's encouraged that most people who recover from the coronavirus have developed antibodies that neutralize the coronavirus in a petri dish.

"Whether that's happening inside the body we don't really know," she cautions.

Research like hers will answer that question, eventually.

But not all antibodies are protective. Iwasaki says some can actually contribute to the disease process and make the illness worse. These antibodies can contribute to inflammation and lead the body to overreact. That overreaction can even be deadly.

"Which types of antibodies protect the host versus those that enhance the disease? We really need to figure that out," she says.

The studies at Yale will follow patients for at least a year, to find out how slowly or quickly immunity might fade. "I wish there was a shortcut," Iwasaki says, "but we may not need to wait a year to understand what type of antibodies are protective."

That's because she and other immunologists are looking for patterns in the immune response that will identify people who have long-term immunity.

Researchers long ago figured out what biological features in the blood (called biomarkers) correlate with immunity to other diseases, says Dr. Kari Nadeau, a pediatrician and immunologist at the Stanford University School of Medicine. She expects researchers will be able to do the same for the new coronavirus.

Nadeau is working on several studies, including one that seeks to recruit 1,000 people who were previously exposed to the coronavirus. One goal is to identify people who produce especially strong, protective antibody responses. She says the antibody-producing cells from those people can potentially be turned into vaccines.

Another critical question she's zeroing in on is whether people who become immune are still capable of spreading the virus.

"Because you might be immune, you might have protected yourself against the virus," she says, "but it still might be in your body and you're giving it to others."

That would have huge public health implications if it turns out people can still spread the disease after they've recovered. Studies from China and South Korea seemed to suggest this was possible, though further studies have cast doubt on that as a significant feature of the disease.

Nadeau is also trying to figure out what can be said about the antibody blood-tests that are now starting to flood the market. There are two issues with these tests. First, a positive test may be a false-positive result, so it may be necessary to run a confirmatory test to get a credible answer. Second, it's not clear that a true positive test result really indicates a person is immune, and if so for how long.

Companies would like to be able to use these tests to identify people who can return to work without fear of spreading the coronavirus.

"I see a lot of business people wanting to do the best for their employees, and for good reason," Nadeau says. "And we can never say you're fully protected until we get enough [information]. But right now we're working hard to get the numbers we need to be able to see what constitutes protection and what does not."

It could be a matter of life or death to get this right. Answers to these questions are likely to come with the accumulation of information from many different labs. Fortunately, scientists around the world are working simultaneously to find answers.

You can contact NPR Science Correspondent Richard Harris at rharris@npr.org.

This content is from Southern California Public Radio. View the original story at SCPR.org.

A llama antibody that fights infections could help humans in the fight against the coronavirus.

New York's Gov. Andrew Cuomo plans to pursue the treatment following its relative success in treating influenza and Ebola.

The post FDA Okays Historic Blood Treatment for COVID; Clinical Trials to Use Antibodies From Recovered Patients appeared first on Good News Network.

The researchers from Queen Mary University of London say the discovery could lead to ground-breaking treatments with “a reduced chance of side effects.”

The post Antibodies Could Be ‘Radically Life-Changing’ New Treatment for OCD and Other Mental Disorders appeared first on Good News Network.

MADONNA said that she has tested positive for CORONAVIRUS antibodies. She went on her “QUARANTINE DIARY” series of INSTAGRAM videos and announced the positive antibody test … more

A method for engineering and utilizing large DNA vectors to target, via homologous recombination, and modify, in any desirable fashion, endogenous genes and chromosomal loci in eukaryotic cells. These large DNA targeting vectors for eukaryotic cells, termed LTVECs, are derived from fragments of cloned genomic DNA larger than those typically used by other approaches intended to perform homologous targeting in eukaryotic cells. Also provided is a rapid and convenient method of detecting eukaryotic cells in which the LTVEC has correctly targeted and modified the desired endogenous gene(s) or chromosomal locus (loci) as well as the use of these cells to generate organisms bearing the genetic modification.

The present invention relates to antibody molecules against anticoagulants, in particular dabigatran, and their use as antidotes of such anticoagulants.

Human antibodies, preferably recombinant human antibodies, that specifically bind to human interleukin-12 (hIL-12) are disclosed. Preferred antibodies have high affinity for hIL-12 and neutralize hIL-12 activity in vitro and in vivo. An antibody of the invention can be a full-length antibody or an antigen-binding portion thereof. The antibodies, or antibody portions, of the invention are useful for detecting hIL-12 and for inhibiting hIL-12 activity, e.g., in a human subject suffering from a disorder in which hIL-12 activity is detrimental. Nucleic acids, vectors and host cells for expressing the recombinant human antibodies of the invention, and methods of synthesizing the recombinant human antibodies, are also encompassed by the invention.

The present disclosure describes antibodies that target HM1.24. In various aspects, the antibodies have specific CDR, variable, or full length sequences, have modifications with the parent antibody, or include at least one modification relative to a parent antibody that alters affinity to an FcγR or alters effector function as compared to the parent antibody. Nucleic acids encoding the antibodies and methods of using the antibodies are also disclosed.

The disclosure relates to anti-glial maturation factor beta (“GMF-B”) monoclonal antibodies (mAbs) and fragments thereof, as well as hybridoma lines that secrete antibodies or fragments. Therapeutic and diagnostic uses of such antibodies, including treatment and detection of cancer and dementia, and methods and kits for detecting cells or samples expressing GMF-B, including soluble GMF-B, are also encompassed.

The present invention relates to novel antibodies, particularly antibodies directed against deletion mutants of epidermal growth factor receptor and particularly to the type III deletion mutant, EGFRvIII. The invention also relates to human monoclonal antibodies directed against deletion mutants of epidermal growth factor receptor and particularly to EGFRvIII. Diagnostic and therapeutic formulations of such antibodies, and immunoconjugates thereof, are also provided.

Monoclonal antibodies (mAbs) having thyroid stimulating activity (TSAb), especially full or considerably agonistic activity, or thyroid blocking activity (TBAb), which are obtainable by genetic immunization of mice, or fragments (F(ab')2, Fab or Fv) or humanized forms of such monoclonal antibodies or single chain forms (SCA; scFv) of such fragments, which antibodies, or their fragments, compete with bovine TSH for epitopes of the human TSHr, compete with autoantibodies from sera from Graves' patients as well as with autoantibodies from sera from patients harboring blocking autoantibodies for epitopes of the human TSHr, bind to conformational epitopes of the human TSHr located in the first 281 amino acids of the human TSHr, and usually also bind to TSFR receptors (TSHr) from different animals. Various uses of such antibodies, or of peptides corresponding to variable regions of such antibodies, are also described and claimed.

The present disclosure provides antibodies, and antigen-binding fragments thereof that bind to EBOV glycoprotein. The present disclosure further provides hybridoma cell lines and methods for making and using the compositions provided herein.

The invention relates to a human Interleukin-2 (hIL-2) specific monoclonal antibody (mAb), or antigen binding fragment thereof, the binding of which to hIL-2 inhibits binding of hIL-2 to CD25 and the antibody is characterized by any of the parameters: the variable chain of the mAb comprises the amino acid sequence of SEQ ID NO 005 or SEQ ID NO 006; the binding to hIL-2 is characterized by a dissociation constant (KD)≦7.5 nmol/L; the binding to hIL-2 is characterized by an off-rate (Koff)≦1×10−4 s−1 and/or the antibody displays no measurable cross-reactivity to murine IL-2.

Cysteine engineered antibodies useful for the site-specific conjugation to a variety of agents are provided. Methods for the design, preparation, screening, selection and use of such antibodies are also provided.

Antibodies that interact with osteoprotegerin ligand (OPGL) are described. Methods of treating osteopenic disorders by administering a pharmaceutically effective amount of antibodies to OPGL are described. Methods of detecting the amount of OPGL in a sample using antibodies to OPGL are described.

The present disclosure provides compositions and methods of use involving binding proteins, e.g., antibodies and antigen-binding fragments thereof, that bind to the matrix metalloproteinase-9 (MMP9) protein (MMP9 is also known as gelatinase-B), such as where the binding proteins comprise an immunoglobulin (Ig) heavy chain (or functional fragment thereof) and an Ig light chain (or functional fragment thereof).

This invention relates to novel monoclonal antibodies that specifically bind to the alpha-folate receptor. In some embodiments, the antibodies inhibit a biological activity of folate receptor-α (FR-α). The antibodies are useful in the treatment of certain cancers, particularly cancers that have increased cell surface expression of the alpha-folate receptor (“FR-α”), such as ovarian, breast, renal, colorectal, lung, endometrial, or brain cancer. The invention also relates to cells expressing the monoclonal antibodies, antibody derivatives, such as chimeric and humanized monoclonal antibodies, antibody fragments, and methods of detecting and treating cancer using the antibodies, derivatives, and fragments.

The present invention provides assays for detecting and measuring the presence or level of anti-TNFα drug therapeutics and autoantibodies in a sample. The present invention is useful for optimizing therapy and monitoring patients receiving anti-TNFα drug therapeutics to detect the presence or level of autoantibodies (e.g., HACA and/or HAHA) against the drug.

In sporadic Alzheimer's disease, neurofibrillary lesion formation is preceded by extensive post-translational modification of the microtubule associated protein tau. Immunoassays have been developed recently that detect tau in biological specimens, thus providing a means for pre-mortem diagnosis of Alzheimer's disease, which has remained elusive. These assays have been improved by the analysis of relevant post-translational modifications, such as phosphorylation, however opportunity for improvement remains. The present invention addresses this issue by disclosing synthetic methylated peptides derived from the tau protein of paired helical filaments and non-diseased control brain. Alzheimer's disease specificity is provided by the presence or absence of methyl moieties on lysine residues and differences between mono-, di-, and tri-methylation. The methylated peptide is useful as an antigen and a binding partner for identifying compounds that interact with the peptide and the methylated tau protein, including antibodies that can distinguish non-diseased brain from that affected by Alzheimer's disease. The resulting antibodies are useful diagnostically and therapeutically. The compounds that specifically bind to methylated tau proteins are useful for eliminating abnormally methylated tau.

Tumor-associated peptide–human leukocyte antigen complexes (pHLAs) represent the largest pool of cell surface–expressed cancer-specific epitopes, making them attractive targets for cancer therapies. Soluble bispecific molecules that incorporate an anti-CD3 effector function are being developed to redirect T cells against these targets using 2 different approaches. The first achieves pHLA recognition via affinity-enhanced versions of natural TCRs (e.g., immune-mobilizing monoclonal T cell receptors against cancer [ImmTAC] molecules), whereas the second harnesses an antibody-based format (TCR-mimic antibodies). For both classes of reagent, target specificity is vital, considering the vast universe of potential pHLA molecules that can be presented on healthy cells. Here, we made use of structural, biochemical, and computational approaches to investigate the molecular rules underpinning the reactivity patterns of pHLA-targeting bispecifics. We demonstrate that affinity-enhanced TCRs engage pHLA using a comparatively broad and balanced energetic footprint, with interactions distributed over several HLA and peptide side chains. As ImmTAC molecules, these TCRs also retained a greater degree of pHLA selectivity, with less off-target activity in cellular assays. Conversely, TCR-mimic antibodies tended to exhibit binding modes focused more toward hot spots on the HLA surface and exhibited a greater degree of crossreactivity. Our findings extend our understanding of the basic principles that underpin pHLA selectivity and exemplify a number of molecular approaches that can be used to probe the specificity of pHLA-targeting molecules, aiding the development of future reagents.

Blood centers are ramping up efforts to collect plasma from people who recovered from COVID-19 in hopes their coronavirus antibodies could save lives.

On the latest episode of "Prime Time," CNN's Chris Cuomo reveals he has recovered from COVID-19 and possesses antibodies. But what does that mean?

Proteins that bind carbohydrate structures can serve as tools to quantify or localize specific glycans in biological specimens. Such proteins, including lectins and glycan-binding antibodies, are particularly valuable if accurate information is available about the glycans that a protein binds. Glycan arrays have been transformational for uncovering rich information about the nuances and complexities of glycan-binding specificity. A challenge, however, has been the analysis of the data. Because protein-glycan interactions are so complex, simplistic modes of analyzing the data and describing glycan-binding specificities have proven inadequate in many cases. This review surveys the methods for handling high-content data on protein-glycan interactions. We contrast the approaches that have been demonstrated and provide an overview of the resources that are available. We also give an outlook on the promising experimental technologies for generating new insights into protein-glycan interactions, as well as a perspective on the limitations that currently face the field.

Ankylosing Spondylitis (AS) is a common, inflammatory rheumatic disease, which primarily affects the axial skeleton and is associated with sacroiliitis, uveitis and enthesitis. Unlike other autoimmune rheumatic diseases, such as rheumatoid arthritis or systemic lupus erythematosus, autoantibodies have not yet been reported to be a feature of AS. We therefore wished to determine if plasma from patients with AS contained autoantibodies and if so, characterize and quantify this response in comparison to patients with Rheumatoid Arthritis (RA) and healthy controls. Two high-density nucleic acid programmable protein arrays expressing a total of 3498 proteins were screened with plasma from 25 patients with AS, 17 with RA and 25 healthy controls. Autoantigens identified were subjected to Ingenuity Pathway Analysis in order to determine patterns of signalling cascades or tissue origin. 44% of patients with Ankylosing Spondylitis demonstrated a broad autoantibody response, as compared to 33% of patients with RA and only 8% of healthy controls. Individuals with AS demonstrated autoantibody responses to shared autoantigens, and 60% of autoantigens identified in the AS cohort were restricted to that group. The AS patients autoantibody responses were targeted towards connective, skeletal and muscular tissue, unlike those of RA patients or healthy controls. Thus, patients with AS show evidence of systemic humoral autoimmunity and multispecific autoantibody production. Nucleic Acid Programmable Protein Arrays constitute a powerful tool to study autoimmune diseases.

Catherine Pihoker
Dec 1, 2005; 54:S52-S61
Section II: Type 1-Related Forms of Diabetes