Bio

Clinical Focus


  • Pediatric Rheumatology

Academic Appointments


Professional Education


  • Board Certification: Pediatrics, American Board of Pediatrics (2002)
  • Residency:Children's Hospital (2002) CA
  • Internship:Children's Hospital (2000) CA
  • Fellowship:Stanford University Medical Center (2005) CA
  • Medical Education:University of Connecticut (1999) CT
  • Board Certification: Pediatric Rheumatology, American Board of Pediatrics (2006)
  • Ph.D., University of Connecticut, Biomedical Science (1999)
  • M.D., University of Connecticut (1999)

Research & Scholarship

Current Research and Scholarly Interests


Pediatric systemic lupus erythematosus;
Autoimmune disease;
Proteomics and autoantigen microarray technology

Publications

Journal Articles


  • Protein microarray analysis reveals BAFF-binding autoantibodies in systemic lupus erythematosus JOURNAL OF CLINICAL INVESTIGATION Price, J. V., Haddon, D. J., Kemmer, D., Delepine, G., Mandelbaum, G., Jarrell, J. A., Gupta, R., Balboni, I., Chakravarty, E. F., Sokolove, J., Shum, A. K., Anderson, M. S., Cheng, M. H., Robinson, W. H., Browne, S. K., Holland, S. M., Baechler, E. C., Utz, P. J. 2013; 123 (12): 5135-5145

    Abstract

    Autoantibodies against cytokines, chemokines, and growth factors inhibit normal immunity and are implicated in inflammatory autoimmune disease and diseases of immune deficiency. In an effort to evaluate serum from autoimmune and immunodeficient patients for Abs against cytokines, chemokines, and growth factors in a high-throughput and unbiased manner, we constructed a multiplex protein microarray for detection of serum factor-binding Abs and used the microarray to detect autoantibody targets in SLE. We designed a nitrocellulose-surface microarray containing human cytokines, chemokines, and other circulating proteins and demonstrated that the array permitted specific detection of serum factor-binding probes. We used the arrays to detect previously described autoantibodies against cytokines in samples from individuals with autoimmune polyendocrine syndrome type 1 and chronic mycobacterial infection. Serum profiling from individuals with SLE revealed that among several targets, elevated IgG autoantibody reactivity to B cell-activating factor (BAFF) was associated with SLE compared with control samples. BAFF reactivity correlated with the severity of disease-associated features, including IFN-?-driven SLE pathology. Our results showed that serum factor protein microarrays facilitate detection of autoantibody reactivity to serum factors in human samples and that BAFF-reactive autoantibodies may be associated with an elevated inflammatory disease state within the spectrum of SLE.

    View details for DOI 10.1172/JCI70231

    View details for Web of Science ID 000327826100020

    View details for PubMedID 24270423

  • Interferon-a induction and detection of anti-ro, anti-la, anti-sm, and anti-rnp autoantibodies by autoantigen microarray analysis in juvenile dermatomyositis. Arthritis and rheumatism Balboni, I., Niewold, T. B., Morgan, G., Limb, C., Eloranta, M., Rönnblom, L., Utz, P. J., Pachman, L. M. 2013; 65 (9): 2424-2429

    Abstract

    Objective. To evaluate serum interferon-alpha (interferon-?) activity in the context of autoantibody profiles in juvenile dermatomyositis (JDM) patients. Methods. Sera from 36 JDM patients were analyzed. Autoantibody profiles were determined by probing microarrays, fabricated with ~80 distinct autoantigens, with serum and a Cy3-conjugated secondary antibody. Arrays were scanned and analyzed to determine antigen reactivity. Serum interferon-? activity was measured using a functional reporter cell assay. Sera were assayed alone or in combination with cellular material released from necrotic U937 cells to stimulate peripheral blood mononuclear cells in vitro from healthy donors, and interferon-? production in culture was measured by a dissociation-enhanced lanthanide fluorescent immunoassay (DELFIA). Results. 75% of JDM sera reacted to at least one of forty-one autoantigens on the microarray, including Ro52, Ro60, La, Smith and ribonucleoprotein (RNP). Seven samples were positive in the reporter cell assay. There was a significant association between reactivity against Ro, La, Smith and proliferating cell nuclear antigen and serum interferon-? activity in this assay (p=0.005). Significance analysis of microarrays (SAM) identified increased reactivity against Smith, RNP, Ro52, U1-C and Mi-2 in these sera. Sixteen samples induced interferon-? production as measured by DELFIA. There was a significant association between reactivity against Ro, La, Smith and RNP and the induction of interferon-? with serum and necrotic cell material (p=0.035). SAM identified increased reactivity against Ro60 in these sera. Conclusion. These data support the hypothesis that nucleic-acid associated autoantibodies, including the Ro/La and Smith/RNP complexes, may stimulate the production of active interferon- ? in children with JDM. © 2013 American College of Rheumatology.

    View details for DOI 10.1002/art.38038

    View details for PubMedID 23740815

  • Type I interferon receptor controls B-cell expression of nucleic acid-sensing Toll-like receptors and autoantibody production in a murine model of lupus ARTHRITIS RESEARCH & THERAPY Thibault, D. L., Graham, K. L., Lee, L. Y., Balboni, I., Hertzog, P. J., Utz, P. J. 2009; 11 (4)

    Abstract

    Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the production of high-titer IgG autoantibodies directed against nuclear autoantigens. Type I interferon (IFN-I) has been shown to play a pathogenic role in this disease. In the current study, we characterized the role of the IFNAR2 chain of the type I IFN (IFN-I) receptor in the targeting of nucleic acid-associated autoantigens and in B-cell expression of the nucleic acid-sensing Toll-like receptors (TLRs), TLR7 and TLR9, in the pristane model of lupus.Wild-type (WT) and IFNAR2-/- mice were treated with pristane and monitored for proteinuria on a monthly basis. Autoantibody production was determined by autoantigen microarrays and confirmed using enzyme-linked immunosorbent assay (ELISA) and immunoprecipitation. Serum immunoglobulin isotype levels, as well as B-cell cytokine production in vitro, were quantified by ELISA. B-cell proliferation was measured by thymidine incorporation assay.Autoantigen microarray profiling revealed that pristane-treated IFNAR2-/- mice lacked autoantibodies directed against components of the RNA-associated autoantigen complexes Smith antigen/ribonucleoprotein (Sm/RNP) and ribosomal phosphoprotein P0 (RiboP). The level of IgG anti-single-stranded DNA and anti-histone autoantibodies in pristane-treated IFNAR2-/- mice was decreased compared to pristane-treated WT mice. TLR7 expression and activation by a TLR7 agonist were dramatically reduced in B cells from IFNAR2-/- mice. IFNAR2-/- B cells failed to upregulate TLR7 as well as TLR9 expression in response to IFN-I, and effector responses to TLR7 and TLR9 agonists were significantly decreased as compared to B cells from WT mice following treatment with IFN-alpha.Our studies provide a critical link between the IFN-I pathway and the regulation of TLR-specific B-cell responses in a murine model of SLE.

    View details for DOI 10.1186/ar2771

    View details for Web of Science ID 000270936400027

    View details for PubMedID 19624844

  • Evaluation of microarray surfaces and arraying parameters for autoantibody profiling PROTEOMICS Balboni, I., Limb, C., Tenenbaum, J. D., Utz, P. J. 2008; 8 (17): 3443-3449

    Abstract

    Autoantigen microarrays are being used increasingly to study autoimmunity. Significant variation has been observed when comparing microarray surfaces, printing methods, and probing conditions. In the present study, 24 surfaces and several arraying parameters were analyzed using >500 feature autoantigen microarrays printed with quill pins. A small subset of slides, including FAST, PATH, and SuperEpoxy2, performed well while maintaining the sensitivity and specificity of autoantigen microarrays previously demonstrated by our laboratory. By optimizing the major variables in our autoantigen microarray platform, subtle differences in serum samples can be identified that will shed light on disease pathogenesis.

    View details for DOI 10.1002/pmic.200800146

    View details for Web of Science ID 000259172400004

    View details for PubMedID 18752214

  • Protein microarrays address the elephant in the room CLINICAL CHEMISTRY Kattah, M. G., Utz, P. J., Balboni, I. 2008; 54 (6): 937-939

    View details for DOI 10.1373/clinchem.2008.104067

    View details for Web of Science ID 000256325800001

    View details for PubMedID 18509011

  • IRF9 and STAT1 are required for IgG autoantibody production and B cell expression of TLR7 in mice JOURNAL OF CLINICAL INVESTIGATION Thibault, D. L., Chu, A. D., Graham, K. L., Balboni, I., Lee, L. Y., Kohlmoos, C., Landrigan, A., Higgins, J. P., Tibshirani, R., Utz, P. J. 2008; 118 (4): 1417-1426

    Abstract

    A hallmark of SLE is the production of high-titer, high-affinity, isotype-switched IgG autoantibodies directed against nucleic acid-associated antigens. Several studies have established a role for both type I IFN (IFN-I) and the activation of TLRs by nucleic acid-associated autoantigens in the pathogenesis of this disease. Here, we demonstrate that 2 IFN-I signaling molecules, IFN regulatory factor 9 (IRF9) and STAT1, were required for the production of IgG autoantibodies in the pristane-induced mouse model of SLE. In addition, levels of IgM autoantibodies were increased in pristane-treated Irf9 -/- mice, suggesting that IRF9 plays a role in isotype switching in response to self antigens. Upregulation of TLR7 by IFN-alpha was greatly reduced in Irf9 -/- and Stat1 -/- B cells. Irf9 -/- B cells were incapable of being activated through TLR7, and Stat1 -/- B cells were impaired in activation through both TLR7 and TLR9. These data may reveal a novel role for IFN-I signaling molecules in both TLR-specific B cell responses and production of IgG autoantibodies directed against nucleic acid-associated autoantigens. Our results suggest that IFN-I is upstream of TLR signaling in the activation of autoreactive B cells in SLE.

    View details for DOI 10.1172/JCI30065

    View details for Web of Science ID 000254588600035

    View details for PubMedID 18340381

  • Systemic hyalinosis: A distinctive early childhood-onset disorder characterized by mutations in the anthrax toxin receptor 2 gene (ANTRX2) PEDIATRICS Shieh, J. T., Swidler, P., Martignetti, J. A., Ramirez, M. C., Balboni, I., Kaplan, J., Kennedy, J., Abdul-Rahman, O., Enns, G. M., Sandborg, C., Slavotinek, A., Hoyme, H. E. 2006; 118 (5): E1485-E1492

    Abstract

    We sought to further characterize the phenotype and facilitate clinical recognition of systemic hyalinosis in children who present with chronic pain and progressive contractures in early childhood.We report on 3 children who presented in infancy with symptoms and signs that initially were not recognized to be those of systemic hyalinosis. Although the children were evaluated for a variety of problems, including lysosomal storage disorders and nonaccidental trauma, all eventually underwent genetic analysis of the anthrax toxin receptor 2 gene (ANTRX2) and were diagnosed as having systemic hyalinosis.We describe the recognizable but variable clinical phenotype of systemic hyalinosis and associated mutations in ANTRX2. Affected individuals presented in early infancy with severe pain and progressive contractures. Initial diagnostic evaluations were unrevealing; however, hyperpigmented skin over bony prominences, skin nodules, and fleshy perianal masses suggested a diagnosis of systemic hyalinosis. ANTRX2 analysis confirmed the diagnosis in each case. Although 2 of the children died in infancy as a result of complications of chronic diarrhea, the third child has survived into midchildhood. These data suggest that some ANTRX2 mutations, such as that identified in the long-term survivor, may be associated with a less severe course of disease.Although some aspects of systemic hyalinosis may resemble lysosomal storage disorders, the clinical features of systemic hyalinosis are distinctive, and detection of an ANTRX2 mutation can confirm the diagnosis. Early recognition of affected individuals should allow for aggressive pain control and expectant management of the multiple associated problems, including gastrointestinal dysfunction.

    View details for DOI 10.1542/peds.2006-0824

    View details for Web of Science ID 000241731700101

    View details for PubMedID 17043134

  • A new two-color Fab labeling method for autoantigen protein microarrays NATURE METHODS Kattah, M. G., Alemi, G. R., Thibault, D. L., Balboni, I., Utz, P. J. 2006; 3 (9): 745-751

    Abstract

    Antigen microarrays hold great promise for profiling the humoral immune response in the settings of autoimmunity, allergy and cancer. This approach involves immobilizing antigens on a slide surface and then exposing the array to biological fluids containing immunoglobulins. Although these arrays have proven extremely useful as research tools, they suffer from several sources of variability. To address these issues, we have developed a new two-color Fab labeling method that allows two samples to be applied simultaneously to the same array. This straightforward labeling approach improves reproducibility and reliably detects changes in autoantibody concentrations. Using this technique we profiled serum from a mouse model of systemic lupus erythematosus (SLE) and detected both expected and previously unrecognized reactivities. The improved labeling and detection method described here overcomes several problems that have hindered antigen microarrays and should facilitate translation to the clinical setting.

    View details for DOI 10.1038/nmeth910

    View details for Web of Science ID 000240290300020

    View details for PubMedID 16929321

  • Multiplexed protein array platforms for analysis of autoimmune diseases ANNUAL REVIEW OF IMMUNOLOGY Balboni, I., Chan, S. M., Kattah, M., Tenenbaum, J. D., Butte, A. J., Utz, P. J. 2006; 24: 391-418

    Abstract

    Several proteomics platforms have emerged in the past decade that show great promise for filling in the many gaps that remain from earlier studies of the genome and from the sequencing of the human genome itself. This review describes applications of proteomics technologies to the study of autoimmune diseases. We focus largely on biased technology platforms that are capable of analyzing a large panel of known analytes, as opposed to techniques such as two-dimensional gel electrophoresis (2DIGE) or mass spectroscopy that represent unbiased approaches (as reviewed in 1). At present, the main analytes that can be systematically studied in autoimmunity include autoantibodies, cytokines and chemokines, components of signaling pathways, and cell-surface receptors. We review the most commonly used platforms for such studies, citing important discoveries and limitations that exist. We conclude by reviewing advances in biomedical informatics that will eventually allow the human proteome to be deciphered.

    View details for DOI 10.1146/annurev.immunol.24.021605.090709

    View details for Web of Science ID 000237583300013

    View details for PubMedID 16551254

  • A sea anemone's environment affects discharge of its isolated nematocysts COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY A-MOLECULAR & INTEGRATIVE PHYSIOLOGY Greenwood, P. G., Balboni, I. M., Lohmann, C. 2003; 134 (2): 275-281

    Abstract

    Nematocysts were isolated from individuals of Calliactis tricolor maintained under different feeding schedules or in different salinities in an attempt to determine how these culture conditions influence the discharge of isolated nematocysts. In addition, the discharge frequencies of nematocysts isolated from two different populations of sea anemones found in two different environments were also compared. Undischarged acontial nematocysts were isolated by extrusion into 1 M sodium citrate and were then treated with 5 mM EGTA to initiate discharge. Nematocysts isolated from anemones maintained under three different feeding schedules showed significantly different responses to the test solution. Nematocysts isolated from anemones maintained in two different salinities did not differ significantly in discharge frequency. Nematocysts isolated from individuals from two separate populations of C. tricolor responded significantly differently to 5 mM EGTA and to deionized water, and these responses also depended upon the isolation solution used. Environmental conditions are known to have an impact on the physiological state of most organisms, but this is the first study providing evidence that the environment or feeding state of an anemone affects discharge of isolated nematocysts. Inherent differences in ionic and osmotic characteristics among nematocysts could explain some of the ambiguities when comparing past studies of isolated nematocyst discharge.

    View details for Web of Science ID 000181525500005

    View details for PubMedID 12547257

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