Salivary gland mucosa-associated lymphoid tissue lymphoma immunoglobulin VH genes show frequent use of V1-69 with distinctive CDR3 features

Salivary gland mucosa associated lymphoid tissue (MALT) type lymphomas are B-cell neoplasms that develop out of a reactive infiltrate, often associated with Sjögren's syndrome. Previous reports from our laboratory involving 10 patients suggested these lymphomas expressed a restricted immunoglobulin (Ig)VH gene repertoire with over use ofV1-69 gene segments. To better determine the frequency ofV1-69 use and whether there may also be selection for CDR3 structures, we sequenced the VH genes from 15 additional cases. Over half of the potentially functionalVH genes (8 of 14) used aVH1 family V1-69 gene segment, whereas the other cases used different gene segments from theVH1 (V1-46),VH3 (V3-7, V3-11, V3-30.3, V3-30.5), and VH4(V4-39) families. The 8 V1-69 VHgenes used 5 different D segments in various reading frames, but all used a J4 joining segment. The V1-69 CDR3s showed remarkable similarities in lengths (12-14 amino acids) and stretches of 2 to 3 amino acids between the V-D and D-J junctions. They did not resemble CDR3s typical of V1-69 chronic lymphocytic leukemias. This study extends our earlier work in establishing that salivary gland MALT lymphomas represent a highly selected B-cell population. Frequent use of V1-69 appears to differ from MALT lymphomas that develop at other sites. The high degree of CDR3 similarity among the V1-69cases suggests that different salivary gland lymphomas may bind similar, if not identical epitopes. Although the antigen specificities are presently unknown, similar characteristic CDR3 sequences are often seen with V1-69 encoded antibodies that have anti-IgG or rheumatoid factor activity.

Salivary gland mucosa-associated lymphoid tissue lymphoma immunoglobulin VH genes show frequent use of V1-69 with distinctive CDR3 features

Salivary gland mucosa associated lymphoid tissue (MALT) type lymphomas are B-cell neoplasms that develop out of a reactive infiltrate, often associated with Sjögren's syndrome. Previous reports from our laboratory involving 10 patients suggested these lymphomas expressed a restricted immunoglobulin (Ig)VH gene repertoire with over use ofV1-69 gene segments. To better determine the frequency ofV1-69 use and whether there may also be selection for CDR3 structures, we sequenced the VH genes from 15 additional cases. Over half of the potentially functionalVH genes (8 of 14) used aVH1 family V1-69 gene segment, whereas the other cases used different gene segments from theVH1 (V1-46),VH3 (V3-7, V3-11, V3-30.3, V3-30.5), and VH4(V4-39) families. The 8 V1-69 VHgenes used 5 different D segments in various reading frames, but all used a J4 joining segment. The V1-69 CDR3s showed remarkable similarities in lengths (12-14 amino acids) and stretches of 2 to 3 amino acids between the V-D and D-J junctions. They did not resemble CDR3s typical of V1-69 chronic lymphocytic leukemias. This study extends our earlier work in establishing that salivary gland MALT lymphomas represent a highly selected B-cell population. Frequent use of V1-69 appears to differ from MALT lymphomas that develop at other sites. The high degree of CDR3 similarity among the V1-69cases suggests that different salivary gland lymphomas may bind similar, if not identical epitopes. Although the antigen specificities are presently unknown, similar characteristic CDR3 sequences are often seen with V1-69 encoded antibodies that have anti-IgG or rheumatoid factor activity.

Plasmodium falciparum Histidine-Rich Protein 2-Based Immunocapture Diagnostic Assay for Malaria: Cross-Reactivity with Rheumatoid Factors

Recently introduced rapid nonmicroscopic immunocapture assays for the diagnosis of malaria infection are being evaluated for their sensitivity and specificity in various epidemiological settings. APlasmodium falciparum histidine-rich protein 2 (PfHRP-2)-based assay (ICT) and a Plasmodium-specific lactate dehydrogenase test (OptiMAL) were evaluated for their specificities in different groups of patients who tested negative for malaria infection by microscopy. The patients were selected from different disease groups: rheumatoid arthritis, hepatitis C, toxoplasmosis, schistosomiasis, and hydatid disease. One hundred thirty-three of the 225 patients were positive for rheumatoid factor. Thirty-five of the 133 (26%) rheumatoid factor-positive patients gave a false-positive reaction with the ICT assay, but only 4 of these gave false-positive reactions with the OptiMAL test. Thirty-three of the 35 false-positive specimens became negative when repeat tested with the ICT assay after absorbing out the rheumatoid factor activity. Our study shows that the PfHRP-2-based ICT assay gave a false-positive reaction in 26% of the patients who had rheumatoid factors, but were negative for malaria by microscopy.

Evaluation of Cryoglobulins

Cryoglobulins are immunoglobulins that precipitate as serum is cooled below core body temperatures. A cryoglobulin screen is the observation of a serum specimen collected and separated while warm for cryoprecipitation over a period of up to 7 days. Values of the screening may be reported as a cryocrit, which is the volume percent of the precipitate compared with the total volume of serum. Further proof that the precipitate is indeed a cryoglobulin can be obtained by demonstrating resolubilization with warming and immunochemical analysis by immunofixation. Detailed characterization of cryoglobulins may also require rigorous washing of the precipitate, quantitation of total protein and immunoglobulins, and evaluation of serum for monoclonal gammopathy, rheumatoid factor activity, evidence of complement activation, and presence of hepatitis C virus seroreactivity or hepatitis C virus RNA. The single most important variable confounding standardization of cryoglobulin testing is the frequently improper separation of warm serum from other blood elements prior to screening and characterization.