Increase of IgA-Bearing Peripheral Blood Lymphocytes in Children With Henoch-Schoenlein Purpura

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    1979;64;918Pediatrics

    Harumi Kuno-Sakai, Hideto Sakai, Yasuo Nomoto, lwao Takakura and Mikio KimuraHenoch-Schoenlein Purpura

    Increase of IgA-Bearing Peripheral Blood Lymphocytes in Children with

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    the World Wide Web at:The online version of this article, along with updated information and services, is located on

    ISSN: 0031-4005. Online ISSN: 1098-4275.

    PrintIllinois, 60007. Copyright 1979 by the American Academy of Pediatrics. All rights reserved.by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village,it has been published continuously since 1948. PEDIATRICS is owned, published, and trademarkedPEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly publication,

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    918 PED IA TR ICS Vo l. 6 4 N o . 6 D ecem ber 1979

    In c reas e o f IgA -B ea rin g P e riph e ra l B loodLym phocy tes in C h ild ren w ith H eno ch .S choen le in P u rpu raHarum i K uno -S aka i, M D , H ide to Saka i, M D , Y asuo Nom oto , MD ,lw ao Takaku ra , M D , and M ik io K im ura , M D

    F ro m th e D e p a rtm e n ts o f P e d ia tr ic s a n d In te rn a l M ed ic ine , T o ka i U n ive rs ity S ch o o l o fM e d ic in e , Is e ha ra , K a n a g a w a , J a p a n

    ABSTRACT . Aberratio n of IgA -bea rin g p e riph era l b loodlym phocy te s in ch ild ren w ith H enoch-S ch oen le in pu r-pu ra has b een investiga ted . E igh teen ch ild ren w ith H en-och-S choen le in pu rpura dem ons tra ted a m ark ed increaseof IgA -bearing lym phocy te s in p eriphe ral b loo d duringthe acu te p hase o f the d isea se . Th e lev els o f IgA -bea ringlym phocy te s re tu rned to th e norm a l lev els a fte r the acu tesym ptom s of H enoch-S choen le in purp ura h ad subs ided .H ow ever, in p atien ts w ho deve lop ed pu rpu ra n ep hritis ,th e in creased leve ls o f IgA -bea rin g lym phocy te s in pe -rip he ra l b lood w ere reta ined afte r the d isappea rance o fpurpu ra , and la sted fo r m ore th an 12 m onths. It is con -c lud ed tha t the m on ito r ing o f IgA -bea rin g p eriphe ralb lood lym phocy te s is use fu l fo r th e sc reen ing o f pa tien tsw it h H e no ch -S ch oe nl ei n purpura and purpura neph ritis .Ped ia tr ic s 64 : 9 18-92 2 , 1979 ; H eno ch -S ch oen le in pur -p ura , purpura nephritis , pe riph era l b loo d lym ph ocy tes ,im m unog lo bu lin A .

    H enoch-S ch oen le in pu rp ura (H SP ) is cha rac te r-ized by non th rom bocy topen ic p urpura , ar th ritis ,abd om in al pa in , and abno rm a litie s in u rina ry sed i-m en ts sim ila r to th ose fo und in po st-s trep to co cca lg lom eru lonep hn tis . S ev era l ab norm a l labo ra to ryfind in gs, su ch as eleva ted strep tococca l an tib odytite rs , eleva ted serum IgA con cen tra tions, an d hy -po album ir iem ia have been desc ribed in HSP . H ow -eve r, su ch abno rm al labo ra to ry find in gs a re no tconsis ten tly observed in ch ild ren w ith H SP . The re-fo re , the m easu rem en ts o f strep to co cca l an tibo dytite rs , se rum IgA concen tra tion s, and se rum a lb u-mm con cen tra tions have little v alu e in th e d iagn osis

    Rece ived fo r p ub lication N ov 19 , 19 78 ; accep ted Apr il 23 , 1979 .Reprin t reques ts to (H .K .S .) D epartm en t o f P ed ia trics , T o ka iU niversity S ch oo l o f M edic ine , Iseh ara, K anagaw a , 25 9-11 , Ja -pan .PED IA TR IC S (ISSN 0031 4005) . Copyrigh t 1979 by theAmerican Academ y of Ped iatric s.

    o f H SP . T he p urpose o f th is stu dy w as to ev alu a teth e poss ib le a ltera tion of IgA -b ea ring lym pho cy tesin ch ild ren w ith H SP and to d iscov er the n atu re o fIgA -bearing lym phocy te s.

    PAT IENTS AND METHODSE igh teen ch ild ren w ith H SP who v isited the o u t-

    pa tien t clin ic o f th e U n ive rs ity H o sp ita l o f theToka i M ed ica l S choo l d u ring 1977 w ere in vesti-ga ted . Am ong these 1 8 pa tien ts , 12 w ere bo ys an dsix w ere g ir ls . T h e age of the pa tien ts ranged be -tw een 3 and 14 yea rs . E lev en of th e 1 8 pa tien ts alsohad som e degree o f h em a tu ria and /o r p ro te inu na(T ab le 1 ). Th e p atien ts w ere stu d ied fo r six to 18m onth s a fte r th e o nse t o f th e H SP sym ptom s. S e-rum imm unog lob u lin lev e ls w ere m easu red by ra -d ia l im m unod iffu sion using the T ri-P a rtigen K it(B eh rin g D iag nos tic s , S om erv ille , N J) . Se rum IgEleve ls w ere m easured by rad io imm unoassay us ingth e Phadebas K it (P ha rm acia D iagn ostic s A B ,U ppsa la , Sw eden ). R ena l b iop sy w as pe rfo rm ed inth ree case s w ith m arked ly abno rm a l u rin ary find -ing s. B iop sy o f the sk in w as p erfo rm ed in th reecases w hich had th e typ ica l H SP rash . P a ren ts an dsib lings of ch ild ren w ith H SP w ere te sted un de r theagreem en t tha t the tests w ou ld b e perfo rm ed toelu cid ate fam ilia l tendenc ie s o f the abn orm a l p op-u la tion of th e lym phocy te s in pe riphe ral b lood .Am bulan t ch ild ren a ttend in g o u tpa tien t c lin ic s w hod id n o t sh ow any clin ica l ev id en ce o f H SP or rena ld iseases and 30 norm al adu lts, 19 to 39 y ea rs o f ag e,w ith ou t any ev id en ce o f imm uno log ic o r rena l d is -eases se rved as a con tro l g ro up .

    ASSAY SYSTEMThe B - an d T -lym pho cy tes w ere cou n ted by th e

    m ethods desc rib ed in th e R epo rt from th e In ter-

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    AR T IC LES 919

    national U nion of Immunological Societi es (IU IS).2I n brief , heparmnized venous blood samples w ereobtained f rom patients and the control group usingphenol - f ree heparmn (Riker, N orthr idge, CA ). L ym-phocy tes w ere separated by the method of B oyum.3Surface I gG-, I gA -, and 1gM -bearing lymphocy tesw ere quanti tated by immunof luorescence using f lu-orescein i sothiocyanate (FITC)-conjugated heavychain speci f i c anti -human I gG , IgA , and 1gM anti -sera f rom goats (FITC/protein rati o: 2.2 to 2.8)(M eloy , Springf i eld, V A ). Fab f racti ons of anti -hu-man IgG, IgA , and 1gM antibody w ere not uti l i zed.Capping was prevented by the addi ti on of 0.02%sodium azide. M onocy tes were identi f i ed by phag-ocy tosi s of l atex beads 0.81 j i n diameter (D i f co,D etroi t, M I ). A l l procedures were perf ormed at 4 C,and lymphocy tes w ere counted by the incident typeof f l uorescent m icroscope (Zeiss, model 9901) usingoi l immersion. The W BC counts ranged betw een5,200 and 8,000/cu mm both in patients and con-trol s. N o relati ve l ymphocy tosi s w as present inei ther group.L ymphocy tes obtained f rom six patients w i thH SP were incubated w i th 2.5 mg of tw ice-crystal -l i zed trypsin (N utr i ti onal B iochem ical Corp, Cleve-land, OH ) per m i l l i l i ter at 37 C f or one hour. A f terthree w ashings w i th RPM I 1640 (GIBCO, GrandIsland, N Y ), the cel l s w ere incubated w i th RPM !1640 at 37 C f or f our hours. The percentages ofIgG-, IgA -, and 1gM -bearing lymphocy tes were de-term ined bef ore and af ter trypsini zati on as wel l asaf ter i ncubation w i th RPM I 1640. T he percentageof T - l ymphocy tes w as measured by E-rosette f or-mation using a method described in the report f romthe IU IS.2

    RESULTSTables 1 and 2 show the resul ts f rom the mea-

    surement of immunoglobul i n-bearing peripheralblood lymphocy tes in chi l dren w i th HSP at thetime of thei r f i rst v i si ts to our cl i ni c. IgA -bearingperipheral blood lymphocy tes w ere markedly in-creased in al l 18 cases of H SP compared w i th thoseof the age-matched control chi l dren (P < .0005).The actual range of I gA -bear ing per ipheral bloodlymphocy tes of those patients w as betw een 8% and2 3% , and the range was betw een 2% and 7% for age-matched control chi l dren. Fig 1 shows the timecourses of I gA -bear ing peripheral blood lympho-cy tes in a chi l d w i th severe purpura nephri ti s andone w i th HSP w i thout any cl i ni cal ev idence ofnephr i ti s. The levels of IgA -bearing peripheralblood lymphocy tes remained high in the patientw i th purpura nephr i ti s f or as long as 12 monthsaf ter the onset of the symptoms (case 1), w hereasin the patient w i th H SP w i thout nephr i ti s (case 18),

    IgA -bearing l ymphocy tes returned to the normallevels w i thin si x months af ter the onset of thesymptoms. I n three other cases w i th prolongedpurpura nephr i ti s (cases 2 to 4), IgA -bearing pe-ri pheral blood lymphocy tes w ere increased f or aslong as 18 months. I n case 3, the disease startedw i th severe intolerable abdom inal pain f ol l ow ed bytarry stools. The IgA -bearing l ymphocy tes in pe-ripheral blood on day 1 accounted for 10% , and thusthe diagnosis of H SP w as feasible pr ior to thedevelopment of the rash. The purpura appeared onday 4, but i t w as very m i ld and disappeared w i thina couple of days. A bnormal urinary f i ndings ap-peared at one w eek af ter the onset of the abdom inalpain. A mong the rest of the 14 HSP cases w i th orw i thout transient nephri ti s, four could not be f ol -l ow ed up and ten cases w ere fol l owed up unti l theI gA -bear ing per ipheral blood lymphocy tes becameless than 7% of the total . The IgA -bearing l ympho-cy tes returned to normal levels w i thin three monthsin th ree cases, w ith in three to si x months in f i vecases, and w i thin nine months in tw o cases.The levels of I gG- and 1gM -bearing peripheralblood lymphocy tes and E-rosette-f orm ing cel l s inchi l dren w i th HSP w ere not signi f i cantl y di f f erentf rom those observed in age-matched control chi l -dren (P values w ere > . 35 , > .15, and > . 25 , r esp ec-tively.)

    A mong the 16 HSP patients tested, serum I gGconcentrati ons w ere elevated in f i ve patients, serumI gA concentrati ons were elevated in nine patients,and serum 1gM concentrati ons were elevated in 13patients. Serum IgE concentrati on was elevated inone patient w ho did not have any history of al l ergi cdi seases. N o signi f i cant correlati ons w ere f ound be-tw een the percentages of I gG-, I gA -, and 1gM -bear-i ng l ymphocy tes and the levels of serum IgG, IgA ,and 1gM concentrati ons, respecti vel y .

    E levated anti streptol ysin 0 ti ters (more than 1:320) were f ound in ten of 17 chi l dren w i th H SP.Serum complement levels remained w i thin normalranges in al l of the 17 H SP cases tested.

    B iopsy specimens f rom the k idneys of the threepatients showed general di f f use prol i f erati v e gb-merubonephr i ti s by hematoxy l i n-eosin staining, andan I gA -dom inant mesangial pattern by immuno-f l uorescent staining. Sk in biopsy specimens of threepatients w i th HSP show ed vascul i ti s i n the upperderm is in al l three cases and deposi ti on of IgAaround the blood vessels in case 12.

    T hi rty normal adul ts showed mean I gG-bear inglymphocy tes, 12.3% w i th SD of 5.9% ; mean I gA -bear ing l ymphocy tes, 3.4% w i th SD of 2.3% ; mean1gM -bear ing lymphocy tes, 4.8% w i th SD of 3.4% ;and mean T -cel l s, 60.1% w i th SD of 11.9% .

    Percentages of IgA -bear ing peripheral blood lym-phocy tes and abnormal i ti es in ur inary f i ndings f or

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    HematuriaProteinuriaHematuriaProteinuriaHema t u n aProteinuria

    HematuriaProteinuria

    ProteinuriaHematuriaHematuriaHematu.riaHematuria

    Proteinuria

    HematuriaNormal

    NormalNo r ma lNormal

    Normal

    Normal

    Normal

    12

    10 Renal biopsy performed

    13 Renal biopsy performed

    81 4182 322

    16

    179 Skin bi opsy per form ed

    139 Skin bi opsy per form ed

    22

    22 Skin biopsy performed

    12

    2 1

    9 2 0 H E NO C H -S C HO E N LE IN P U R P U R A

    TAB LE 1 . Clinical Symptoms and Initial L aborato ry Results of Ch ildren with Henoch-Sc hoenlein PurpuraCase N o. A ge Sex Signs and Urinary IgA-Bearing Comments

    (yr) Symptoms Findings Lymphocytes (% )1 7 M Purpura

    Abdominal pain2 6 M Purpura

    Abdominal painTarry stool

    3 5 F PurpuraAbdominal painT arry stool

    4 1 4 M Pu r p u r aAbdominal painBloody stoolSubcutaneous nodule

    5 9 F Purpura6 8 M Purpura7 5 M Purpura8 9 F U rticaria9 4 M Purpura

    ArthritisBleeding into scrotum

    10 3 M PurpuraArthritisA bdominal pain

    11 9 F Purpura12 4 M Purpura

    ArthritisVomiting

    13 9 F Purpura14 7 M Purpura15 10 F Purpura

    Abdominal painVomiting

    16 9 M Purpura and urticariaEpistaxisNauseaAbdominal painArthritis

    17 4 M PurpuraArthritisQuinke s edema

    18 6 M PurpuraAr t h r i t i s

    14 Renal biopsy performed

    TA B LE 2 . Subpopulations of Peripheral Blood Lym-phocytes from Children with Henoch-Schoenlein Pur-pura and from Those of the Control Group*

    H enoch-Schoen- Controllem PurpuraImmunogbobulin-bear-

    ing cells (% )IgG 12.7 6.5 11.8 8.5IgA 15.3 5.1 4.5 1.31gM 15.2 8.5 12.6 7.6

    T -cells (%) 39.1 12.5 38.4 19.1* V alues given are means SD .

    the probands and their families are summarized inFig 2. I gA -bearing lymphocytes were increased insome of the siblings and parents. Among thosefamily members who had increased IgA -bearingper iphera l blood lymphocytes, several showed mi-croscopic hematuria.

    Table 3 indicates that trypsinization of lympho-cytes obtained from the patients removed surfaceimmunogbobulins almost completely. A fter fourhours of incubation with RPM I 1640, the cell sur-face I gA was restored, and in four cases, the per-centages of the restored I gA -bearing lymphocyteswere less than those before trypsinization, and intwo cases, more IgA -bearing lymphocytes were ob-served after the incubation than before trypsimza-tion.D I S C U S S I O N

    D iagnosis of HSP or purpura nephritis has beenperformed according to clinical manifestations suchas purpura, abdominal pain, arthralgia or abnormalurinary findings. However, when abdominal pain isthe main symptom, the diagnosis of HSP is diff icult.Furthermore, when a patient w ith purpura nephri-

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    w>.

    0I0.>.- JzUiP

    a IIENOCH-SCHOENLEIN I NCR E A SED IG A-B AR IN G L YM PH OC YTES* t : i M IC RO SC OP IC H ER AT UR IA

    i I DECEASEDC # { 1 4 9 } : l DIVORCED;. : NOT S ARP L E D

    ART ICLES 921

    0 3 6 9 12MONTH S

    F ig 1 . Time course s o f the IgA -bearing lymphocy te s inperipheral blood o fchildren w ith Henoch-S choenle in pur-pura. So lid c irc le s indicate the values w ith purpura ne-phntis (case 1 ). Open circ le s indicate the v alues w ithHenoch-Scho enle in purpura but w ithout nephritis (case18 ) . Shadow ed area indicates the range o f the ag e-matched contro l children.

    LJTR 7 -c .1 . 1 T g. j 1 2 j 38 /. 181 . ll. 3# {1 49}/. 2 !. 2 3 1 .

    10. 11 . * 1 2 .D T O E J -r-O5#{149} / . 6 ! . 2 , / . I 3/ a .2 Il

    16! . 8 ! . 17 ! . 9 ! .

    14 . L imO0! . I 17 / .

    16 .

    I 15E2!.

    #{149}

    DO. i .J6! .b2u38 ! . 22 ! .

    17 .

    L:19 ! .

    0r . I IJI_. !) /#{149}b28 ! .

    18k . . ,L..i-- ___1__! :I.a :]21 ! .

    F ig 2 . Kindreds w ith Henoch-S choenle in purpura pro -bands.

    tis is seen after all o ther acute symptoms o f HSPhave subsided, the diagnosis is sometimes difficultw ithout a renal biopsy . Prev iously , w e reported thatIgA -bearing peripheral blood lymphocytes w ere in-creased in patients w ith IgA -IgG mesang ial ne-phropathy as w e ll as in those w ith benign recurrenthematuria.4 5 Among chronic g lomerubonephritis o fvarious forms, there are only three diseases in w hichIgA -bearing peripheral blood lymphocytes are spe-cif ically increased, ie , purpura nephritis , IgA -IgGmesangial nephropathy , and benign recurrent he-maturia. Those diseases are c linically sim ilar in thathematuria is the main symptom. Prev ious reportssugg es ted that both IgA -IgG mesangial nephropa-thy and purpura nephritis show identical histopath-o log ic findings in renal bio psy spec imens .6 Identif i-

    TABLE 3 . Treatment w ith Trypsin o f the IgA -B earingLymphocytes from Peripheral B lood o f Children w ithHenoch-Schoenle in Purpura

    IgA-Bearing Lymphocyte s (%)Case N o. .B efore Trypsin A fter Trypsin A fter

    D igestion D igestion Incubation8 21 0 297 1 9 0 915 18 0 351 1 1 7 1 73 1 0 1 917 9 1 8

    cation of antig ens in those tw o diseases as w ell asin benign recurrent hematuria w ill e luc idate howclo se ly the diseases are interre lated. Prelim inaryobservations w ith patients w ith po st-s treptoco ccalg lomerulonephritis show ed poly clonal increases inimmunoglobulin-bearing lymphocy tes (H. Kuno-Sakai, H. Sakai, Y . N omo to e t al, unpublisheddata).

    The increase of IgA -bearing lymphocytes in pe-ripheral blood of the familie s o f certain probands iso f interest. The underly ing causes of the increase ofIgA -bearing peripheral blo od lymphocy tes both inprobands and the ir familie s are unknown. How ever,it is fasc inating to postulate that some fam ilies w ithincreased leve ls o f IgA -bearing lymphocytes aremore prone to respond eas ily to certain antig enicstimulations and hence dev elop HSP or latentlycarry m icroscopic hematuria, w hile others are un-responsive to the same s timulations and remain freeof the diseases.

    S ince there w as neither leukopenia no r relativeneutrophiia, increases in the percentages of im-munog lobulin-bearing peripheral blood lympho-cytes re flec ted the abso lute increase in these ce lls .The IgA -bearing lymphocytes w e observed w erethose w hich carried IgA on the ir cell surfaces.There fore, w hat w e have counted was the sum ofIgA -produc ing lymphocy tes and lymphocy tesw hich had cy tophilic IgA attached.

    A s shown in Table 3 , the surface IgA w as re -moved almo st comple te ly by digestion w ith trypsin.D uring the incubation period, lymphocytes thatw ere capable of produc ing IgA accumulated IgA ontheir ce ll surfaces. Some IgA produced de novom ight have become attached to other lymphocytes.There fore, IgA -bearing lymphocytes observ ed afterincubation represented mainly IgA -produc ing lym-phocytes as w e ll as some lymphocy tes that had IgAattached. The increase in IgA -bearing peripheralblood lymphocy tes in HSP patients may no t besimply explained by increased serum IgA leve ls inHSP patients s ince there w as not a direc t co rrela-tion betw een peripheral blood IgA -bearing lympho-cytes and serum IgA leve ls . It is probable thatcytophilic IgA in patients w ith HSP is increased,

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    922 HENOCH -SCHOENLE IN PURPURA

    resul ti ng in the increased IgA -bearing per ipheralblood lymphocy tes. A l though the rati os betw eenperipheral blood IgA -producing lymphocy tes andlymphocy tes w i th cy tophi i c I gA may vary f rompatient to patient, the measurement of peripheralblood IgA -bearing l ymphocy tes i s useful cl i ni cal l yin the diagnosis of H SP. The I gG- and 1gM -bearinglymphocy tes w ere higher both in patients and incontrol s w hen compared w i th the usual standards.B ecause of the technique w e used, there w as apossibi l i ty that some lymphocy tes had IgG or 1gMattached. H owever, thi s does not af f ect the cl i ni calsigni f i cance of the measurements of IgA -bearingl ymphocy tes in patients w i th possible H SP.

    Deposi ti on of IgA in the glomerular mesangiumand sk in of patients w i th H SP has been reported.7 8I t has been noted that I gA -containing cryogbobul i nwas observed characteri sti cal l y in 12 of 34 H SPpatients.9 In addi ti on to the above-mentioned resul tthat I gA is associated w i th H SP, our resul ts indi catethat IgA -bear ing peripheral blood lymphocy tes arealso related to HSP and purpura nephri ti s. Furtherstudies are warranted to determ ine w hether these

    I gA antibodies share identi cal antigenic speci f i ci -ties.R E F E R E NC E S1. Si lber D L : H enoch-Schoenlein syndrome. P e d ia tr C lin

    No r t h A m 19:1061, 19722. I nternat ional U nion of Immunological Soci eties (IU IS) Re-

    port: I denti f i cati on, enumerati on and i solati on of B and Tl ymphocy tes f rom human per ipheral blood. C lin Im m un o lI mmu n o p a t h o l 3:584, 1975

    3. B oyum A : Separat ion of leucocy tes f rom blood and bonemarrow. S can d J C lin La b Inve st 21 (suppl 97):1, 1968

    4. N omoto Y , Sakai H , A rimori 5: I ncrease of I gA -beari ngl ymphocy tes in peri pheral blood f rom pati ents w i th I gAnephropathy. A m J C lin P a th o l 71:158, 1979

    5. N omoto Y , Sakai H , A rimori 5, et a! : Immunopathologicaland hi stol ogi cal studies on benign recurrent hematur ia: C l in-i copathol ogi cal sim i lari t i es w i th I gA nephropathy . Am JPatho l 94:51, 1979

    6. Jenis EH , L ow enthal DT : K idn ey B io psy In terp re ta tio n .Phi l adelphia, FA Dav is Co, 1977, pp 114-124, 169-178

    7. B aart de la Fai l l e-K uyper EH , K ater L , K ooi ker CJ, et al :I gA -deposi ts in cutaneous bl ood-v essel w al l s and mesangi umi n H en och -Sch# {2 46} n lei n sy ndr om e. La n c e t 1:892, 1973

    8. Giangiacomo J, T sai CC : D ermal and glomerular deposi t i onof I gA in anaphy lactoi d purpura. Am J Di s Chi ld 131:981,1977

    9. Garcia-Fuentes M , Chantler C , W i l l i ams DG : Cryoglobul i -nem ia i n H enoch-Sch#{ 246} nl ei n purpura. B r M e d J 2:163, 1977

    FAM ILY H ISTOR IES NOT ALW AYS H IGHLY REGARDED IN BOSTON

    A n unusual f am i l y hi story w as mentioned in the week ly Cl ini copathobogicalExerci se publ i shed in the December 14, 1978 issue of T he N ew E ng la nd Jou rna lo fM ed i c i ne (Case 49-1978). A w oman w i th Sjogren s syndrome and histi ocy ti cl ymphoma of the brain had a f ather w ho died of a brain tumor and a son w hodied of leukem ia. I n a letter to the edi tor (Purti o D , et ad: N E ng i J M ed 300:797, 1975) , Purti o et al complained that no attention was paid to thi s unusualhi story in the ten-page report. I n thei r opinion the inf ormation meri ted relevantlaboratory (tests) and accurate and imaginati ve analysi s. E.P. Richardson, Jrof the M assachusetts General H ospi tal repl i ed that, al though important tocancer gen e tics , the f am i l y hi story w as only on e of many i tems of data in thediagnosti c ( ! ) evaluation. (T hus w as explorati on of a clue to cause dism issed inf avor of detai l s about diagnosis, as i f both w ere not part of cl ini cal m edi ci ne.)

    Robert W . M i l l er, M DNational Cancer I nsti tute-N IHBethesda, M D 20205

    From C hildho od C ancer Et io logy N ew sle tte r # 58 , M ay 15, 1979.

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    ART ICLES 945

    ACKNOWLEDGMENTSThis work was supported in part by National Institutes

    of Health grants NH LBI 19185 and NH LBI 07159.W e thank D r J. W . Severinghaus and M s M ary Staf-

    ford for technical assistance and advice throughout thes t u d y .

    REFERENCES1. Huch R, Lubbers DW , Huch A : Quantitative continuous

    measurement of partial oxygen pressure on the skin of adultsand newborn babies. P flu ieg ers A rch 337:185, 19722. Peabody JL , Gregory GA , W illis M M , et al: T ranscutaneous

    oxygen tension in sick infants. A m R ev R esp ir D is 118:83,1978

    3. Fenner A , M uller R, Busse HG, et al: T ranscutaneous deter-mination of arterial oxygen tension. Ped ia trics 55:224, 1975

    4. Severinghaus JW , Stafford M , Bradley A F: T cPCO2 elec-trode design, calibration, and temperature gradient prob-

    ERRA TA

    lems. A cta A n ae sthe sio l S ca nd 68: 1 1 8, 19785. D eleted in proof6. Fenn W O, H ahn H (eds): H andbo ok o fPh ysio logy , S ection

    3: Resp ira t ion . Washington, DC, A merican Physi ologicalSociety, 1964, vol 2, p 479

    7. Eberhard P, M indt W : Reliability of cutaneous oxygen mea-surement by skin sensors w ith large-size cathodes. ActaA na esthes io l Sc and 68:20, 1978

    8. V ersmold HT , H olzmann M , L inderkamp 0, et al: Skinoxygen permeabili ty in premature infants. Ped ia trics 62:488,1978

    9. Thunstrom AM , Severinghaus JW : T he use of concentratedN aHO3 in TcPO2 electrodes to diminish 02 consumption anddehydration drift. A cta A nae sth esio l Sca nd 68:55, 1978

    10. Severinghaus JW , Stafford M , Thunstrom AM : Estimationof skin metabolism and blood f low with T cPO2 and TcPCO2electrodes by cuff occlusion of the circulation. A cta A nae s-the sio l Sca nd 68:9, 197 8

    11. Tusiewicz K , M oldofsky H , Bryan AC, et a! : M echanics ofthe rib cage and diaphragm during sleep. J A pp i P hy sio l 43:600, 1977

    In the article Infectious M ononucleosis and Encephalitis: Recovery of EBV irus from Spinal Fluid by H alsted and Chang (Pediatr ics 64:257-258, 1979),reference 9 should be added as follows: Rocchi F, de Felici A , Ragona G, et al:Quantitative evaluation of Epstein-Barr-virus-infected mononuclear peripheralb l o o d leukocytes in infectious mononucleosis. N E ng i J M ed 296:132, 1977. Onpage 258, f irst column, 12 lines from bottom, reference 5 should read reference9 .

    I n the article Folic Acid Supplementation in Low Birth W eight Infants, byStevens et al (Pediatr ics 64:333-335, 1979) two corrections were received afterthe journal went to press. In T able 1, RCF values should read ng/ml not g/ml.On page 335, f irst column, line 21, RCF levels should read less than 100 ng/mlnot 100 g/mi.

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    1979;64;918PediatricsHarumi Kuno-Sakai, Hideto Sakai, Yasuo Nomoto, lwao Takakura and Mikio Kimura

    Henoch-Schoenlein PurpuraIncrease of IgA-Bearing Peripheral Blood Lymphocytes in Children with

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